Metabolomics Standards Initiative Ontology (MSIO) 1.0 OWL http://creativecommons.org/licenses/by/3.0/ Silvia Marin Vitaly Selivanov Marta Cascante Pedro Ramon de Atauri Carulla Teresa Fan an application ontology for supporting description and annotation of mass-spectrometry and nmr-spectroscopy based metabolomics experiments and fluxomics studies. Andrew Lane Hunter Moseley Philippe Rocca-Serra Alejandra Gonzalez-Beltran has part An object property linking a consent code to a specific restriction which further constrains it, such as research should be restricted to a specific disease or geographical location. DUO:0000010 is restricted to This document is about information artifacts and their representations is_about is a (currently) primitive relation that relates an information artifact to an entity. 7/6/2009 Alan Ruttenberg. Following discussion with Jonathan Rees, and introduction of "mentions" relation. Weaken the is_about relationship to be primitive. We will try to build it back up by elaborating the various subproperties that are more precisely defined. Some currently missing phenomena that should be considered "about" are predications - "The only person who knows the answer is sitting beside me" , Allegory, Satire, and other literary forms that can be topical without explicitly mentioning the topic. person:Alan Ruttenberg Smith, Ceusters, Ruttenberg, 2000 years of philosophy is about a chemical entity is said to be an isotopomer of another one if it has the same number of each isotopic atom but differs in their positions. isotopomer is a contraction of isotopic isomer CH2DCH=0 is isotopomer of CH3CD=0 IUPAC compendium of chemical terminology (2nd edition, 1997) is isotopomer of CH4 is isotopologue of CH3D which is isotopologue of CH2D2 a molecular entity which differs only in isotopic composition (i.e the number of isotopic substitution differs but the overall chemical structure is unchanged) is said to be an isotologue Philippe Rocca-Serra IUPAC compendium of chemical terminology (2nd edition, 1997) is isotopologue of A relation associating a product to its manufacturer. Alejandra Gonzalez-Beltran Philippe Rocca-Serra manufactured by has_specified_input is_specified_input_of has_specified_output has_role entity Entity Julius Caesar Verdi’s Requiem the Second World War your body mass index BFO 2 Reference: In all areas of empirical inquiry we encounter general terms of two sorts. First are general terms which refer to universals or types:animaltuberculosissurgical procedurediseaseSecond, are general terms used to refer to groups of entities which instantiate a given universal but do not correspond to the extension of any subuniversal of that universal because there is nothing intrinsic to the entities in question by virtue of which they – and only they – are counted as belonging to the given group. Examples are: animal purchased by the Emperortuberculosis diagnosed on a Wednesdaysurgical procedure performed on a patient from Stockholmperson identified as candidate for clinical trial #2056-555person who is signatory of Form 656-PPVpainting by Leonardo da VinciSuch terms, which represent what are called ‘specializations’ in [81 Entity doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example Werner Ceusters 'portions of reality' include 4 sorts, entities (as BFO construes them), universals, configurations, and relations. It is an open question as to whether entities as construed in BFO will at some point also include these other portions of reality. See, for example, 'How to track absolutely everything' at http://www.referent-tracking.com/_RTU/papers/CeustersICbookRevised.pdf An entity is anything that exists or has existed or will exist. (axiom label in BFO2 Reference: [001-001]) entity Entity doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example Werner Ceusters 'portions of reality' include 4 sorts, entities (as BFO construes them), universals, configurations, and relations. It is an open question as to whether entities as construed in BFO will at some point also include these other portions of reality. See, for example, 'How to track absolutely everything' at http://www.referent-tracking.com/_RTU/papers/CeustersICbookRevised.pdf per discussion with Barry Smith An entity is anything that exists or has existed or will exist. (axiom label in BFO2 Reference: [001-001]) continuant Continuant An entity that exists in full at any time in which it exists at all, persists through time while maintaining its identity and has no temporal parts. BFO 2 Reference: Continuant entities are entities which can be sliced to yield parts only along the spatial dimension, yielding for example the parts of your table which we call its legs, its top, its nails. ‘My desk stretches from the window to the door. It has spatial parts, and can be sliced (in space) in two. With respect to time, however, a thing is a continuant.’ [60, p. 240 Continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example, in an expansion involving bringing in some of Ceuster's other portions of reality, questions are raised as to whether universals are continuants A continuant is an entity that persists, endures, or continues to exist through time while maintaining its identity. (axiom label in BFO2 Reference: [008-002]) if b is a continuant and if, for some t, c has_continuant_part b at t, then c is a continuant. (axiom label in BFO2 Reference: [126-001]) if b is a continuant and if, for some t, cis continuant_part of b at t, then c is a continuant. (axiom label in BFO2 Reference: [009-002]) if b is a material entity, then there is some temporal interval (referred to below as a one-dimensional temporal region) during which b exists. (axiom label in BFO2 Reference: [011-002]) (forall (x y) (if (and (Continuant x) (exists (t) (continuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [009-002] (forall (x y) (if (and (Continuant x) (exists (t) (hasContinuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [126-001] (forall (x) (if (Continuant x) (Entity x))) // axiom label in BFO2 CLIF: [008-002] (forall (x) (if (Material Entity x) (exists (t) (and (TemporalRegion t) (existsAt x t))))) // axiom label in BFO2 CLIF: [011-002] continuant (forall (x) (if (Continuant x) (Entity x))) // axiom label in BFO2 CLIF: [008-002] (forall (x) (if (Material Entity x) (exists (t) (and (TemporalRegion t) (existsAt x t))))) // axiom label in BFO2 CLIF: [011-002] Continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. For example, in an expansion involving bringing in some of Ceuster's other portions of reality, questions are raised as to whether universals are continuants A continuant is an entity that persists, endures, or continues to exist through time while maintaining its identity. (axiom label in BFO2 Reference: [008-002]) if b is a continuant and if, for some t, c has_continuant_part b at t, then c is a continuant. (axiom label in BFO2 Reference: [126-001]) if b is a continuant and if, for some t, cis continuant_part of b at t, then c is a continuant. (axiom label in BFO2 Reference: [009-002]) if b is a material entity, then there is some temporal interval (referred to below as a one-dimensional temporal region) during which b exists. (axiom label in BFO2 Reference: [011-002]) (forall (x y) (if (and (Continuant x) (exists (t) (continuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [009-002] (forall (x y) (if (and (Continuant x) (exists (t) (hasContinuantPartOfAt y x t))) (Continuant y))) // axiom label in BFO2 CLIF: [126-001] ic IndependentContinuant a chair a heart a leg a molecule a spatial region an atom an orchestra. an organism the bottom right portion of a human torso the interior of your mouth A continuant that is a bearer of quality and realizable entity entities, in which other entities inhere and which itself cannot inhere in anything. b is an independent continuant = Def. b is a continuant which is such that there is no c and no t such that b s-depends_on c at t. (axiom label in BFO2 Reference: [017-002]) For any independent continuant b and any time t there is some spatial region r such that b is located_in r at t. (axiom label in BFO2 Reference: [134-001]) For every independent continuant b and time t during the region of time spanned by its life, there are entities which s-depends_on b during t. (axiom label in BFO2 Reference: [018-002]) (forall (x t) (if (IndependentContinuant x) (exists (r) (and (SpatialRegion r) (locatedInAt x r t))))) // axiom label in BFO2 CLIF: [134-001] (forall (x t) (if (and (IndependentContinuant x) (existsAt x t)) (exists (y) (and (Entity y) (specificallyDependsOnAt y x t))))) // axiom label in BFO2 CLIF: [018-002] (iff (IndependentContinuant a) (and (Continuant a) (not (exists (b t) (specificallyDependsOnAt a b t))))) // axiom label in BFO2 CLIF: [017-002] independent continuant b is an independent continuant = Def. b is a continuant which is such that there is no c and no t such that b s-depends_on c at t. (axiom label in BFO2 Reference: [017-002]) For any independent continuant b and any time t there is some spatial region r such that b is located_in r at t. (axiom label in BFO2 Reference: [134-001]) For every independent continuant b and time t during the region of time spanned by its life, there are entities which s-depends_on b during t. (axiom label in BFO2 Reference: [018-002]) (forall (x t) (if (IndependentContinuant x) (exists (r) (and (SpatialRegion r) (locatedInAt x r t))))) // axiom label in BFO2 CLIF: [134-001] (forall (x t) (if (and (IndependentContinuant x) (existsAt x t)) (exists (y) (and (Entity y) (specificallyDependsOnAt y x t))))) // axiom label in BFO2 CLIF: [018-002] (iff (IndependentContinuant a) (and (Continuant a) (not (exists (b t) (specificallyDependsOnAt a b t))))) // axiom label in BFO2 CLIF: [017-002] disposition Disposition an atom of element X has the disposition to decay to an atom of element Y certain people have a predisposition to colon cancer children are innately disposed to categorize objects in certain ways. the cell wall is disposed to filter chemicals in endocytosis and exocytosis BFO 2 Reference: Dispositions exist along a strength continuum. Weaker forms of disposition are realized in only a fraction of triggering cases. These forms occur in a significant number of cases of a similar type. b is a disposition means: b is a realizable entity & b’s bearer is some material entity & b is such that if it ceases to exist, then its bearer is physically changed, & b’s realization occurs when and because this bearer is in some special physical circumstances, & this realization occurs in virtue of the bearer’s physical make-up. (axiom label in BFO2 Reference: [062-002]) If b is a realizable entity then for all t at which b exists, b s-depends_on some material entity at t. (axiom label in BFO2 Reference: [063-002]) (forall (x t) (if (and (RealizableEntity x) (existsAt x t)) (exists (y) (and (MaterialEntity y) (specificallyDepends x y t))))) // axiom label in BFO2 CLIF: [063-002] (forall (x) (if (Disposition x) (and (RealizableEntity x) (exists (y) (and (MaterialEntity y) (bearerOfAt x y t)))))) // axiom label in BFO2 CLIF: [062-002] disposition b is a disposition means: b is a realizable entity & b’s bearer is some material entity & b is such that if it ceases to exist, then its bearer is physically changed, & b’s realization occurs when and because this bearer is in some special physical circumstances, & this realization occurs in virtue of the bearer’s physical make-up. (axiom label in BFO2 Reference: [062-002]) If b is a realizable entity then for all t at which b exists, b s-depends_on some material entity at t. (axiom label in BFO2 Reference: [063-002]) (forall (x t) (if (and (RealizableEntity x) (existsAt x t)) (exists (y) (and (MaterialEntity y) (specificallyDepends x y t))))) // axiom label in BFO2 CLIF: [063-002] (forall (x) (if (Disposition x) (and (RealizableEntity x) (exists (y) (and (MaterialEntity y) (bearerOfAt x y t)))))) // axiom label in BFO2 CLIF: [062-002] realizable RealizableEntity the disposition of this piece of metal to conduct electricity. the disposition of your blood to coagulate the function of your reproductive organs the role of being a doctor the role of this boundary to delineate where Utah and Colorado meet A specifically dependent continuant that inheres in continuant entities and are not exhibited in full at every time in which it inheres in an entity or group of entities. The exhibition or actualization of a realizable entity is a particular manifestation, functioning or process that occurs under certain circumstances. To say that b is a realizable entity is to say that b is a specifically dependent continuant that inheres in some independent continuant which is not a spatial region and is of a type instances of which are realized in processes of a correlated type. (axiom label in BFO2 Reference: [058-002]) All realizable dependent continuants have independent continuants that are not spatial regions as their bearers. (axiom label in BFO2 Reference: [060-002]) (forall (x t) (if (RealizableEntity x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (bearerOfAt y x t))))) // axiom label in BFO2 CLIF: [060-002] (forall (x) (if (RealizableEntity x) (and (SpecificallyDependentContinuant x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (inheresIn x y)))))) // axiom label in BFO2 CLIF: [058-002] realizable entity To say that b is a realizable entity is to say that b is a specifically dependent continuant that inheres in some independent continuant which is not a spatial region and is of a type instances of which are realized in processes of a correlated type. (axiom label in BFO2 Reference: [058-002]) All realizable dependent continuants have independent continuants that are not spatial regions as their bearers. (axiom label in BFO2 Reference: [060-002]) (forall (x t) (if (RealizableEntity x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (bearerOfAt y x t))))) // axiom label in BFO2 CLIF: [060-002] (forall (x) (if (RealizableEntity x) (and (SpecificallyDependentContinuant x) (exists (y) (and (IndependentContinuant y) (not (SpatialRegion y)) (inheresIn x y)))))) // axiom label in BFO2 CLIF: [058-002] sdc SpecificallyDependentContinuant Reciprocal specifically dependent continuants: the function of this key to open this lock and the mutually dependent disposition of this lock: to be opened by this key of one-sided specifically dependent continuants: the mass of this tomato of relational dependent continuants (multiple bearers): John’s love for Mary, the ownership relation between John and this statue, the relation of authority between John and his subordinates. the disposition of this fish to decay the function of this heart: to pump blood the mutual dependence of proton donors and acceptors in chemical reactions [79 the mutual dependence of the role predator and the role prey as played by two organisms in a given interaction the pink color of a medium rare piece of grilled filet mignon at its center the role of being a doctor the shape of this hole. the smell of this portion of mozzarella A continuant that inheres in or is borne by other entities. Every instance of A requires some specific instance of B which must always be the same. b is a relational specifically dependent continuant = Def. b is a specifically dependent continuant and there are n > 1 independent continuants c1, … cn which are not spatial regions are such that for all 1 i < j n, ci and cj share no common parts, are such that for each 1 i n, b s-depends_on ci at every time t during the course of b’s existence (axiom label in BFO2 Reference: [131-004]) b is a specifically dependent continuant = Def. b is a continuant & there is some independent continuant c which is not a spatial region and which is such that b s-depends_on c at every time t during the course of b’s existence. (axiom label in BFO2 Reference: [050-003]) Specifically dependent continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. We're not sure what else will develop here, but for example there are questions such as what are promises, obligation, etc. (iff (RelationalSpecificallyDependentContinuant a) (and (SpecificallyDependentContinuant a) (forall (t) (exists (b c) (and (not (SpatialRegion b)) (not (SpatialRegion c)) (not (= b c)) (not (exists (d) (and (continuantPartOfAt d b t) (continuantPartOfAt d c t)))) (specificallyDependsOnAt a b t) (specificallyDependsOnAt a c t)))))) // axiom label in BFO2 CLIF: [131-004] (iff (SpecificallyDependentContinuant a) (and (Continuant a) (forall (t) (if (existsAt a t) (exists (b) (and (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))))))) // axiom label in BFO2 CLIF: [050-003] specifically dependent continuant b is a relational specifically dependent continuant = Def. b is a specifically dependent continuant and there are n > 1 independent continuants c1, … cn which are not spatial regions are such that for all 1 i < j n, ci and cj share no common parts, are such that for each 1 i n, b s-depends_on ci at every time t during the course of b’s existence (axiom label in BFO2 Reference: [131-004]) b is a specifically dependent continuant = Def. b is a continuant & there is some independent continuant c which is not a spatial region and which is such that b s-depends_on c at every time t during the course of b’s existence. (axiom label in BFO2 Reference: [050-003]) Specifically dependent continuant doesn't have a closure axiom because the subclasses don't necessarily exhaust all possibilites. We're not sure what else will develop here, but for example there are questions such as what are promises, obligation, etc. per discussion with Barry Smith (iff (RelationalSpecificallyDependentContinuant a) (and (SpecificallyDependentContinuant a) (forall (t) (exists (b c) (and (not (SpatialRegion b)) (not (SpatialRegion c)) (not (= b c)) (not (exists (d) (and (continuantPartOfAt d b t) (continuantPartOfAt d c t)))) (specificallyDependsOnAt a b t) (specificallyDependsOnAt a c t)))))) // axiom label in BFO2 CLIF: [131-004] (iff (SpecificallyDependentContinuant a) (and (Continuant a) (forall (t) (if (existsAt a t) (exists (b) (and (IndependentContinuant b) (not (SpatialRegion b)) (specificallyDependsOnAt a b t))))))) // axiom label in BFO2 CLIF: [050-003] site Site Manhattan Canyon) a hole in the interior of a portion of cheese a rabbit hole an air traffic control region defined in the airspace above an airport the Grand Canyon the Piazza San Marco the cockpit of an aircraft the hold of a ship the interior of a kangaroo pouch the interior of the trunk of your car the interior of your bedroom the interior of your office the interior of your refrigerator the lumen of your gut your left nostril (a fiat part – the opening – of your left nasal cavity) b is a site means: b is a three-dimensional immaterial entity that is (partially or wholly) bounded by a material entity or it is a three-dimensional immaterial part thereof. (axiom label in BFO2 Reference: [034-002]) (forall (x) (if (Site x) (ImmaterialEntity x))) // axiom label in BFO2 CLIF: [034-002] site b is a site means: b is a three-dimensional immaterial entity that is (partially or wholly) bounded by a material entity or it is a three-dimensional immaterial part thereof. (axiom label in BFO2 Reference: [034-002]) (forall (x) (if (Site x) (ImmaterialEntity x))) // axiom label in BFO2 CLIF: [034-002] gdc GenericallyDependentContinuant The entries in your database are patterns instantiated as quality instances in your hard drive. The database itself is an aggregate of such patterns. When you create the database you create a particular instance of the generically dependent continuant type database. Each entry in the database is an instance of the generically dependent continuant type IAO: information content entity. the pdf file on your laptop, the pdf file that is a copy thereof on my laptop the sequence of this protein molecule; the sequence that is a copy thereof in that protein molecule. A continuant that is dependent on one or other independent continuant bearers. For every instance of A requires some instance of (an independent continuant type) B but which instance of B serves can change from time to time. b is a generically dependent continuant = Def. b is a continuant that g-depends_on one or more other entities. (axiom label in BFO2 Reference: [074-001]) (iff (GenericallyDependentContinuant a) (and (Continuant a) (exists (b t) (genericallyDependsOnAt a b t)))) // axiom label in BFO2 CLIF: [074-001] generically dependent continuant b is a generically dependent continuant = Def. b is a continuant that g-depends_on one or more other entities. (axiom label in BFO2 Reference: [074-001]) (iff (GenericallyDependentContinuant a) (and (Continuant a) (exists (b t) (genericallyDependsOnAt a b t)))) // axiom label in BFO2 CLIF: [074-001] immaterial ImmaterialEntity BFO 2 Reference: Immaterial entities are divided into two subgroups:boundaries and sites, which bound, or are demarcated in relation, to material entities, and which can thus change location, shape and size and as their material hosts move or change shape or size (for example: your nasal passage; the hold of a ship; the boundary of Wales (which moves with the rotation of the Earth) [38, 7, 10 immaterial entity A disease is a disposition (i) to undergo pathological processes that (ii) exists in an organism because of one or more disorders in that organism. [url:http://ontology.buffalo.edu/medo/Disease_and_Diagnosis.pdf ] DOID:4 disease A data item that is used to indicate consent permissions for datasets and/or materials, and relates to the purposes for which datasets and/or material might be removed, stored or used. DUO:0000001 consent code A categorical data item indicating the primary category the consent code belongs to according to Dyke et al. 2016. DUO:0000002 consent code primary category A categorical data item indicating the secondary category the consent code belongs to according to Dyke et al. 2016. DUO:0000003 consent code secondary category This consent code primary category indicates there is no restriction on use. DUO:0000004 Note: the NRES alternative term may be confusing as in the UK it also stands for National Research Ethics Service no restriction This primary category consent code indicates that use is allowed for health/medical/biomedical purposes and other biological research, including the study of population origins or ancestry. DUO:0000005 general research use and clinical care This primary category consent code indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry. DUO:0000006 health/medical/biomedical research and clinical care This primary category consent code indicates that use is allowed provided it is related to the specified disease. DUO:0000007 disease-specific research and clinical care This primary category consent code indicates that use of the data is limited to the study of population origins or ancestry. population origins/ancestry research DUO:0000011 population origins or ancestry research This secondary category consent code indicates that use is limited to studies of a certain research type. DUO:0000012 research-specific restrictions This secondary category consent code indicates that use is limited to research purposes (e.g., does not include its use in clinical care). DUO:0000014 research use only This secondary category consent code indicates that use includes methods development research(e.g., development of software or algorithms) only within the bounds of other use limitations. DUO:0000015 no general methods research This secondary category consent code indicates that use is limited to genetic studies only (i.e., no phenotype-only research) DUO:0000016 genetic studies only Requirements indicate additional conditions set for use. DUO:0000017 data use requirements This requirement indicates that use is limited to not-for-profit organizations. DUO:0000018 not-for-profit use only This requirement indicates that requestor agrees to make results of studies using the data available to the larger scientific community. DUO:0000019 publication required This requirement indicates that the requestor must agree to collaboration with the primary study investigator(s). DUO:0000020 collaboration required This requirement indicates that the requestor must provide documentation of local IRB/ERB approval. DUO:0000021 ethics approval required This requirement indicates that use is limited to within a specific geographic region. DUO:0000022 geographical restriction This requirement indicates that requestor agrees not to publish results of studies until a specific date publication embargo DUO:0000024 publication moratorium This requirement indicates that use is approved for a specific number of months. DUO:0000025 time limit on use This requirement indicates that use is limited to use by approved users. DUO:0000026 user-specific restriction This requirement indicates that use is limited to use within an approved project. DUO:0000027 project-specific restriction This requirement indicates that use is limited to use within an approved institution. DUO:0000028 institution-specific restriction This requirement indicates that the requestor must return derived/enriched data to the database/resource. DUO:0000029 RTN return to database/resource geographic location A reference to a place on the Earth, by its name or by its geographical location. GAZ:00000448 geographic location data item Data items include counts of things, analyte concentrations, and statistical summaries. a data item is an information content entity that is intended to be a truthful statement about something (modulo, e.g., measurement precision or other systematic errors) and is constructed/acquired by a method which reliably tends to produce (approximately) truthful statements. 2/2/2009 Alan and Bjoern discussing FACS run output data. This is a data item because it is about the cell population. Each element records an event and is typically further composed a set of measurment data items that record the fluorescent intensity stimulated by one of the lasers. 2009-03-16: data item deliberatly ambiguous: we merged data set and datum to be one entity, not knowing how to define singular versus plural. So data item is more general than datum. 2009-03-16: removed datum as alternative term as datum specifically refers to singular form, and is thus not an exact synonym. 2014-03-31: See discussion at http://odontomachus.wordpress.com/2014/03/30/aboutness-objects-propositions/ JAR: datum -- well, this will be very tricky to define, but maybe some information-like stuff that might be put into a computer and that is meant, by someone, to denote and/or to be interpreted by some process... I would include lists, tables, sentences... I think I might defer to Barry, or to Brian Cantwell Smith JAR: A data item is an approximately justified approximately true approximate belief PERSON: Alan Ruttenberg PERSON: Chris Stoeckert PERSON: Jonathan Rees data data item information content entity Examples of information content entites include journal articles, data, graphical layouts, and graphs. A generically dependent continuant that is about some thing. 2014-03-10: The use of "thing" is intended to be general enough to include universals and configurations (see https://groups.google.com/d/msg/information-ontology/GBxvYZCk1oc/-L6B5fSBBTQJ). information_content_entity 'is_encoded_in' some digital_entity in obi before split (040907). information_content_entity 'is_encoded_in' some physical_document in obi before split (040907). Previous. An information content entity is a non-realizable information entity that 'is encoded in' some digital or physical entity. PERSON: Chris Stoeckert OBI_0000142 information content entity OpenFLUX2 is a MATLAB-based modelling software for 13C metabolic flux analysis (MFA). Modern techniques like Elementary Metabolite Unit (EMU) framework, are implemented for efficient computing of fluxes. OpenFlux2 is an expanded version of OpenFLUX to support analysis of parallel labeling experiments (PLE) data, i.e. those experiments using several different tracers concomitantly. Philippe Rocca-Serra https://doi.org/10.1186/s12934-014-0152-x openFlux2 2H2O -> 2H2+ O2 a process which uses or consumes chemical/molecular entities to generate other molecular entities Philippe Rocca-Serra adapted from wikipedia: https://en.wikipedia.org/wiki/Chemical_reaction last accessed: 2018-01-11 chemical reaction buffer role is a role played by a chemical solution to dampens pH variation Philippe Rocca-Serra EU H2020 PhenoMenAl buffer role derivatization agent role is a role played by a chemical entity involved in a chemical reaction known as derivatization whereby another chemical entity is augmented, but not altered otherwise, with groups specify to the chemical entity acting as a derivatization agent. Philippe Rocca-Serra EU H2020 PhenoMenAl derivatization agent role external standard role is a role played by a material entity used as a reference point for signal acquisition. this is a type of positive control role Philippe Rocca-Serra EU H2020 PhenoMenAl external standard role internal standard role is a role played by a chemical entity added in known amount to an analytical sample Philippe Rocca-Serra EU H2020 PhenoMenAl internal standard role long term reference role is a role played by a material entity known for its stability to provide the means to compare across sets of acquisitions Philippe Rocca-Serra EU H2020 PhenoMenAl long term reference role positive control role is a role played by a material entity in the context of analytical work to provide no signal or a signal as close to baseline as technically possible (within the limits of detection) thereby providing a reference point for the noise and indicative that the detectors and signal acquisition system operate nominally. Philippe Rocca-Serra EU H2020 PhenoMenAl negative control role positive control role is a role played by a material entity in the context of analytical work to provide a signal of known intensity indicative that the detectors and signal acquisition system operate nominally. Philippe Rocca-Serra EU H2020 PhenoMenAl positive control role solvent role is a role played by a chemical entity present in a solution and providing the solvatation activity to other compounds, the solutes. Philippe Rocca-Serra EU H2020 PhenoMenAl solvent role AbsoluteIDQ p150 kit is a reagent system manufactured by Biocrates AG, Austria which allows the targeted metabolite profiling of up to 163 distinct molecular entities with quantitative accuracy on human plasma samples. Philippe Rocca-Serra http://www.biocrates.com/products/research-products/absoluteidq-p150-kit AbsoluteIDQ p150 Kit AbsoluteIDQ p180 kit is a reagent system manufactured by Biocrates AG, Austria which allows the targeted metabolite profiling of up to 188 distinct endogenous molecular entities with quantitative accuracy from 5 different compound classes (i.e. acylcarnitines, amino acids, hexoses, phospho- and sphingolipids and biogenic amines). The assay requires very small sample amounts (10 μL) and shows excellent reproducibility. Philippe Rocca-Serra http://www.biocrates.com/products/research-products/absoluteidq-p180-kit AbsoluteIDQ p180 Kit AbsoluteIDQ Stero17 kit is a reagent system manufactured by Biocrates AG, Austria which allows the targeted metabolite profiling (identification and quantification) of 17 steroid hormones (sex steroids, mineralocorticoids, glucocorticoids). Philippe Rocca-Serra http://www.biocrates.com/products/research-products/absoluteidq-p150-kit AbsoluteIDQ Stero17 Kit AbsoluteIDQ p400 kit is a reagent system manufactured by Biocrates AG, Austria which allows the targeted metabolite profiling of up to 400 distinct molecular entities with quantitative accuracy on human plasma samples. Philippe Rocca-Serra http://www.biocrates.com/products/research-products/absoluteidq-p400-hr-kit AbsoluteIDQ p400 Kit ammonium bicarbonate is kind of buffer solution where the weak base is ammonium and the weak acid carbonic acid. Philippe Rocca-Serra cosmos tracer based metabolomics working group ammonium bicarbonate buffer the bicarbonate buffering system is used to regulate the pH of blood. A buffer solution (more precisely, pH buffer or hydrogen ion buffer) is an aqueous solution consisting of a mixture of a weak acid and its conjugate base, or vice versa. Philippe Rocca-Serra https://en.wikipedia.org/wiki/Buffer_solution buffer a dilution series sample is a material entity which is part of a collection of such materials, each defined by its dilution factor with respect to a stock solution of reference sample. Dilution series samples are used to assess the linearity of the signal acquisition by providing a set of expected and known quantities. Philippe Rocca-Serra EU H2020 PhenoMenAl dilution series reference Fetal bovine serum (FBS) or fetal calf serum (spelled foetal in Commonwealth English) is a material entity which correspsonds to the blood fraction remaining after the natural coagulation of blood, followed by centrifugation to remove any remaining red blood cells. Philippe Rocca-Serra cosmos tracer based metabolomics working group https://en.wikipedia.org/wiki/Fetal_bovine_serum fetal bovine serum HEPES buffer is a buffer which uses HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) as a zwitterionic organic chemical buffering agent . Philippe Rocca-Serra cosmos tracer based metabolomics working group HEPES buffer a pooled sample made from fractions from samples collected from large, study independent collection of samples with the purpose of serving as a reference for quality control purpose. Long Term Reference Samples maybe used in ring trials to check cross facility data acquisition consistency but also to enable data integration, irrespective of data acquisition platform or study context but providing a single point of reference against which to normalize. purpose: Inter study variability(within a core facility) Alejandra Gonzalez-Beltran Philippe Rocca-Serra LTR biological pool (inter) [CEA] biological pool [MASTR-MS] inter study QC H2020 PhenoMenal long term reference Phosphated buffer saline (PBS) buffer is a buffer which is a water-based salt solution containing disodium hydrogen phosphate, sodium chloride and, in some formulations, potassium chloride and potassium dihydrogen phosphate. Philippe Rocca-Serra cosmos tracer based metabolomics working group https://en.wikipedia.org/wiki/Phosphate-buffered_saline PBS buffer quality control material (qc material) is a material entity which is used for the purpose to quality control processes such as assessing unwanted source of variations during signal acquisitions. Typically, these materials are known compounds or mixture of compounds introduced in known quantities into test samples or run as is, diluted from stock to provide reference measurements at fixed temporal intervals. Philippe Rocca-Serra QC material EU H2020 PhenoMenAl quality control material a reference compound is a chemical entity of know origin, formula and established spectral fingerprint added to a solution of unknown component in known quantities in order to provide a basis (hence the term reference) with which to establish a comparison, be used for calibration or quality control or quantitation estimate for unknown compound in spectral analysis such as NMR or mass spectrometry Philippe Rocca-Serra pure standard reference material cosmos tracer based metabolomics working group reference compound NIST reference material: https://www.nist.gov/publications/certification-standard-reference-materialr-968f-fat-soluble-vitamins-frozen-human-serum a reference compound mix is a material entity which consists of composite solution of several molecular entities acting as reference compound and present in known quantity in the mixture, with which to establish a comparison, be used for calibration or quality control or quantitation estimate for unknown compound in spectral analysis such as NMR or mass spectrometry Philippe Rocca-Serra pure standard mix reference material mix cosmos tracer based metabolomics working group reference compound mix a material entity corresponding to a sample containing no biological sample, which undergoes all laboratory process of preparation as used for test samples and used as a negative control to evaluate contamination effect and artefacts caused by reactions occurring during the sample preparation steps of test samples. method blank method reference sample preparation blank a material entity corresponding to ‘solvent’ (mobile phase in chromatography context) only, containing no biological sample and used as a negative control to evaluate carry over effect between injections of test samples. Alejandra Gonzalez-Beltran Philippe Rocca-Serra normal blank [Leiden] solvent blank solvent blank a study reference sample is a pool made up of aliquots from all the sample collected in a given study. It is meant to be used to monitor intra study variability, also known as within study variability of the signal acquisition, for instance between batches of such data acquisition. Alejandra Gonzalez-Beltran Philippe Rocca-Serra SR iQC - internal quality control [Imperial College London] study reference study reference material a carrier gas is a chemical entity in gaseous phase with is used for eluting chemical compound in a gas chromatography process. Philippe Rocca-Serra cosmos tracer based metabolomics working group carrier gas tert-Butyldimethylsilyl chloride is a derivatization agent a derivatization agent is a chemical entity which is used in a material combination process known as derivatization and which consists in adding chemical groups to a molecule in an attempt to make it more volatile and therefore amenable to gas-chromatography mass spectrometry. Philippe Rocca-Serra EU H2020 PhenoMenAl derivatization agent Philippe Rocca-Serra QDA reagent quaternary ammonium dodecyl aminooxy reagent an isotopic tracer is a molecular entity whose atoms may have entirely or partially replaced with isotopes of the normally occuring element and which can be distinguished from naturally occuring molecular entity through mass analysis or nucleic magnetic resonance analysis. Philippe Rocca-Serra cosmos tracer based metabolomics working group isotopic tracer a specificly labeled isotopic tracer is an isotopic tracer where only specific positions on the backbone have been replaced with an isotopic atom. Such molecules are often used in Fluxomics analysis and metabolic path elucidation experiments. Philippe Rocca-Serra cosmos tracer based metabolomics working group positionally labeled isotopic tracer uniformly labeled isotopic tracer is an isotopic tracer where all atoms of the backbone are replaced with the same isotope. Such molecules are often used in Fluxomics analysis and metabolic path elucidation experiments. Philippe Rocca-Serra cosmos tracer based metabolomics working group uniformly labeled isotopic tracer A single isotopologue represents a set of mass-equivalent isotopomers. It is therefore a set of chemicals representing molecules of the same chemical entity and same isotopic composition. Isotopologue can be monitored using mass spectrometry but only NMR spectroscopy can discriminate between positional isotopomer. Philippe Rocca-Serra adapted from IUPAC nomenclature cosmos tracer based metabolomics working group isotopologue OpenFLUX is a MATLAB-based modelling software for 13C metabolic flux analysis (MFA). Modern techniques like Elementary Metabolite Unit (EMU) framework, are implemented for efficient computing of fluxes. Philippe Rocca-Serra https://www.ncbi.nlm.nih.gov/pubmed/19409084 openFlux a mass isotopomer (short for isotopic isomer) is a compound which differ from another one only by the position of an isotopic substitution in the molecular backbone. One in a collection of isomers with the same number of each isotope of each element but differing in their positions within the chemical structure. Philippe Rocca-Serra isotopic isomer mass isotopomer cosmos tracer based metabolomics working group isotopomer a solvent is a chemical entity playing a solvent role in a solution. Philippe Rocca-Serra solvent A non-radioactive, glucose molecule in which all six carbons are substituted with stable carbon 13 (13C) isotope, with potential imaging application or fluxomics studies. CAS RN 110187-42-3 submit to CHEBI Philippe Rocca-Serra uniformly-labeled [U-13C] glucose http://www.cancer.gov/drugdictionary?cdrid=739239 an isotopomer where the isotopic content of specific atoms is known for a part of the molecule should it be a relation or a class? Philippe Rocca-Serra partial isotopomer metabolic flux unit is a measurement unit datum used to qualify a metabolic flux. It is therefore an amount of matter over a temporal interval. Philippe Rocca-Serra Philippe Rocca-Serra for the COSMOS-Fluxomics Ontology (CFO) metabolic flux unit micromolar per milligram of protein per hour is a unit used to report metabolic fluxes. it denotes a measurement indicative of an amount of material over a period of time and normalized to the amount of protein present in the cellular fraction under consideration Philippe Rocca-Serra umol mg prot-1 hr-1 micromolar per milligram of protein per hour c13Fluc2 is a software suite of applications for the detailed quantification of intracellular (quasi) steady-state fluxes as explored by 13C-based metabolic flux analysis. The tool is developed and maintained by W. Wiechert at the Institute of Bio- and Geosciences, IBG-1: Biotechnology and JARA High Performance Computing, Forschungszentrum, Julich GmbH, 52428 Julich, Germany. Philippe Rocca-Serra Weitzel M, Nöh K, Dalman T, Niedenführ S, Stute B, Wiechert W 13CFLUX2 - High-Performance Software Suite for 13C-Metabolic Flux Analysis Bioinformatics 2012 doi: 10.1093/bioinformatics/bts646 http://www.13cflux.net/13cflux2/ 13cflux2 C13 is a tool for quantification of in vivo metabolic fluxes, from carbon labelling experiments. The underlying approach is metabolic flux analysis based on stationary carbon isotope labelling experiments, using fractional enrichment data. The mathematical framework adopted herein is the one developed by Wiechert and de Graaf (1997). It is developed and maintained at the Chalmers University of Technology, Department of Chemical and Biological Engineering, Systems Biology group , Kemivägen 10 412 96 Göteborg, Sweden. Philippe Rocca-Serra http://129.16.106.142/tools.php?c=c13 C13 An intuitive tool for quantitative investigations of intracellular metabolism by users that are not familiar with numerical methods or isotopic tracer experiments. The aim of this open source software is to enable non-specialists to adapt the software to their specific scientific interests, including other 13C-substrates, labeling mixtures, and organisms. FiatFlux is written in Matlab Philippe Rocca-Serra http://www.ncbi.nlm.nih.gov/pubmed/16122385 fiatFlux FIA is a software written in python, implementing the FIA (Fluxomer Iterative Algorithm) - a new effective method for 13C metabolic fluxes (tracer) experiments analysis. It is developed by Orr Srour, Jamey D. Young and Yonina C. Eldar at the Technion, Israel Institute of Technology Philippe Rocca-Serra FIA https://doi.org/10.1186/1752-0509-5-129 Fluxomer Iterative Algorithm iMAT is a software integrating transcriptomic and proteomic data with genome-scale metabolic network models to predict enzyme metabolic flux. The tool is developed by Tomer Shlomi at The Isreal Institute of Technology Philippe Rocca-Serra Integrative Metabolic Analysis Tool Bioinformatics (2010) 26 (24): 3140-3142. https://doi.org/10.1093/bioinformatics/btq602 http://www.cs.technion.ac.il/~tomersh/methods.html iMAT INCA: a computational platform for isotopically non-stationary metabolic flux analysis, Jamey D. Young. Bioinformatics, first published online January 11, 2014. INCA is a software package that can perform both steady-state metabolic flux analysis and isotopically non-stationary metabolic flux analysis. The software provides a framework for comprehensive analysis of metabolic networks using mass balances and elementary metabolite unit balances. The generation of balance equations and their computational solution is completely automated and can be performed on networks of arbitrary complexity. Philippe Rocca-Serra Isotopomer Network Compartmental Analysis http://www.ncbi.nlm.nih.gov/pubmed/24413674 INCA Iso2Flux is a Python-based flux analysis software that allows to perform 13C Metabolic Flux Analysis on a sub-network of a large scale model. Iso2flux uses constraint-based modelling to compute steady state fluxes across a large metabolic network and uses such flxues to predict 13C distribution across a subser of the newtork. Then, given a set of 13C data Iso2flux can iteratively find the steady state flux distributions that are most consistent with such fluxes. the source code is available from: https://github.com/cfoguet/iso2flux http://portal.phenomenal-h2020.eu/app-library/iso2flux https://github.com/cfoguet/iso2flux Pedro de Atauri Vitaly Selivanov iso2flux “Isodyn” is a C++-program that performs an analysis of stable isotope tracer data to assess metabolic flux profiles in living cells. Isodyn simulates the dynamics of isotopic isomer (isotopomer) distribution in central metabolic pathways, and, by changing its parameters, which reflect the characteristics of corresponding biochemical reactions, fit the simulated dynamics of mass isotopomers to that observed experimentally. The simulated metabolic fluxes that correspond to the best fit are assumed to reproduce the real fluxes in the analyzed biological object and conditions. Isodyn contains tools that check the goodness of fit and perform a statistical analysis of obtained metabolic fluxes. the source code is available from: https://github.com/seliv55/isodyn Philippe Rocca-Serra http://portal.phenomenal-h2020.eu/app-library/isodyn Pedro de Atauri Vitaly Selivanov isodyn IsoDesign, a software that enables these parameters to be maximized by optimizing the isotopic composition of the label input. It can be applied to (13) C-MFA investigations using a broad panel of analytical tools (MS, MS/MS, (1) H NMR, (13) C NMR, etc.) individually or in combination. It includes a visualization module to intuitively select the optimal label input depending on the biological question to be addressed. The software is available from: http://metasys.insa-toulouse.fr/software/isodes/ Philippe Rocca-Serra https://doi.org/10.1002/bit.24997 isodesign Metran is a software for Metabolic Flux Analysis implementing the Elementary Metabolite Units. Metabolic Flux Analysis (MFA) has emerged as a tool of great significance for metabolic engineering and quantitative cell physiology. An important limitation of MFA, as carried out via stable isotope labeling and GC-MS measurements, is the large number of isotopomer/cumomer equations that need to be solved, especially when multiple isotopic tracers are used for the labeling of the system. This restriction reduces the ability of MFA to fully utilize the power of multiple isotopic tracers in elucidating the physiology of realistic situations comprising complex bioreaction networks. To address this limitation, we have developed a novel framework for modeling of isotopic tracer distributions that significantly reduces the number of variables, without any loss of information. The EMU framework is based on a highly efficient decomposition method that identifies the minimum amount of information needed to simulate isotopic labeling within a reaction network using the knowledge of atomic transitions occurring in the network reactions. The functional units generated by the decomposition algorithm, called elementary metabolite units (EMUs), form the new basis for generating system equations that describe the relationship between fluxes and isotopomer abundances. The EMU decomposition algorithm is completely unsupervised and converges within seconds even for very genome-wide network models. Isotopomer abundances simulated using the EMU framework are identical to those obtained using the isotopomer and cumomer frameworks, however, requiring significantly less computation time. For a typical carbon labeling system the total number of equations that needs to be solved is reduced by one order-of-magnitude (100s EMUs vs. 1000s cumomers). As such, the EMU framework is most efficient for the analysis of labeling by multiple isotopic tracers. For example, the analysis of gluconeogenesis network model with 2H, 13C, and 18O tracers requires only 354 EMUs compared to >2,000,000 isotopomers Philippe Rocca-Serra http://www.ncbi.nlm.nih.gov/pubmed/17088092 metran “midcor.R” is an “R”-program that performs a primary analysis of isotopic isomers (isotopomers) distribution obtained by Gas Chromatography coupled with Mass Spectrometry (GCMS). The aim of this analysis is to have a correct distribution of isotopes originated from substrates that are artificially enriched with specific isotopes (usually 13C). To this end the program performs a correction for natural occurring isotopes and also correction for “impurities” of the assay media that give peaks overlapping with the spectra of analyzed labeled metabolites. This program offers two ways of corrections of “impurities” resulted from overlapping the assayed mass isotopomer distribution with peaks produced either by unknown metabolites in the media, or by different fragments produced by the assayed metabolite. The source code is available from https://github.com/seliv55/midcor Philippe Rocca-Serra http://portal.phenomenal-h2020.eu/app-library/midcor Pedra de Atauri Vitaly Selivanov midcor an isotopically non-stationary labeling experiment is a material processing used in fluxomics studies where cells cultures are grown in the presence of radiolabeled tracer compound for relatively short amount of time and samples collection before the system can reach an isotopic and metabolic steady state, and is therefore in a non-stationary phase. Such experiment are shorter to run that steady-state labeling experiment and usually allow to determine fluxes with increased precision. Alejandra Gonzalez-Beltran Philippe Rocca-Serra EU H2020 PhenoMenAl non-stationary isotopic labeling experiment A non-radioactive, glutamine molecule in which 5 carbons are substituted with stable carbon 13 (13C) isotope and both glutamin nitrogen atoms are substituted with 15N ones, with potential imaging application or fluxomics studies. submit to CHEBI Alejandra Gonzalez-Beltran Philippe Rocca-Serra 184161-19-1 13C5-15N2-glutamine OpenMoebius is an integrated software for conventional 13C-Metabolic Flux Analysis and isotopically nonstationary 13C-Metabolic Flux Analysis (INST-13C-MFA). This work is partially supported by JST, Strategic International Collaborative Research Program, SICORP for JP-US Metabolomics. Philippe Rocca-Serra http://www-shimizu.ist.osaka-u.ac.jp/hp/en/software/OpenMebius.html openMoebius RaMID is a computer program designed to read the machine-generated files saved in netCDF format containing registered time course of m/z chromatograms. It evaluates the peaks of mass isotopomer distribution (MID) making them ready for further correction for natural isotope occurrence. RaMID is written in “R”, uses library “ncdf4” (it should be installed before the first use of RaMID) and contains several functions, located in the files “ramid.R” and "libcdf.R," designed to read CDF files, and analyze and visualize the spectra that they contain. the source code is available from: https://github.com/seliv55/RaMID Philippe Rocca-Serra https://github.com/seliv55/RaMID Pedro de Atauri Vitaly Selivanov ramid a software produced by Nicolas Zamboni and colleagues for flux ratio estimation based on a 5 step workflow known as SUMOFLUX and which relies on surrogate modeling. Matlab code available from: http://www.imsb.ethz.ch/research/zamboni/resources.html Philippe Rocca-Serra http://ncbi.nlm.nih.gov/pubmed/27626798 sumoflux The chemical compounds of a living cell are connected by biochemical reactions which convert one compound into another. The reactions are catalyzed by enzymes. Thus, all compounds in a cell are parts of an intricate biochemical network of reactions which is called metabolic network. It is possible to use network analyses to infer how selection acts on metabolic pathways. Philippe Rocca-Serra adapted from wikipedia: https://en.wikipedia.org/wiki/Biological_network network a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reactions catalyzed by enzymes. Philippe Rocca-Serra https://en.wikipedia.org/wiki/Metabolic_pathway pathway CH4 + 2 O2 → CO2 + 2 H2O, the stoichiometric coefficient of CH4 is -1, the stoichiometric coefficient of O2 is -2, for CO2 it would be +1 and for H2O it is +2 a stoichiometric coefficient is an information object which is part of an equation describing a chemical reaction and which corresponds to the number of molecules of a reactant taking part in a reaction. Philippe Rocca-Serra http://en.wikipedia.org/wiki/Stoichiometry#Stoichiometric_coefficient stoichiometric coefficient the amount of time elapsed for a cell culture to growth twice its initial size, usually expressed in hour Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group cell culture doubling time Cell seeding density is a measurement datum which denotes the number of cells per surface area in the case of adherent cells or number of cells per volume in the case of free cells deposited in the culture vessel to start a cell culture. The cell seeding density is therefore stated in number of cells per cm2 or number of cells per ml. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group cell seeding density average cell volume is a measurement datum used to report over physcal occupancy of cells under study. This information is used for as input for kinetic modeling. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group cell volume when cells reach 50% confluence level, replenish medium confluence level is a measurement datum denotes the status of a cell culture and how cells are occupying the space available in a plate. confluence levels are stated in %. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group confluence level dilution factor is a measurement data item which indicates in percentage the level of purity of a material in the context of dilution such as a dilution series. Philippe Rocca-Serra EU H2020 PhenoMenAl dilution factor the amount of dideoxyribonucleic acids present in a cell culture or tissue. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group DNA content intracellular metabolite average content is a measurement provided of metabolite concentration normalized against cell average volume or DNA content or protein content or dry weight Philippe Rocca-Serra metabolite content EU H2020 PhenoMenAl cosmos tracer based metabolomics working group Barcelona meeting, march 2015 interacellular metabolite average content the concentration of a molecular entity acting as metabolite and stated in standard concentration units, such molar, micromolar and so on Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolite concentration metabolite pool size estimate is an information entity used in fluxomics studies to estimate the amount of molecular entity available to a particular metabolic process. It is usually reported in umol per mg of protein. can be also computed from simulation and be output of such simulation (then provide confidence indicator) Alejandra Gonzalez-Beltran Philippe Rocca-Serra pool size EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolite pool size estimate passage number is a measurement data item denoting how many times a cell culture has been split and transferred to a new culture vessel. It can also be considered to be equivalent to how many times a cell culture has reached 100% confluence Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group passage number ratio of protein content over a reference standard element (usually bovine serum albumin (BSA)) Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group protein concentration the amount of (soluble) protein from cell culture or tissue. the quantity of total protein recovered from an extraction process varies depending on the solvent and buffers used during the extraction phase. the amount is usuall expressed in milligram (refer to Unit Ontology) Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group protein content signal intensity is a kind of measurement providing an estimate of the strength of a phenomena as it is recorded. For digital detector instrument, the signal intensity is usually a electric intensity or a field strength of the electromagnetic wave transmitting a signal. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group signal intensity Signal intensity of all m/z values at the maximum of the peak (also known as maximum signal intensity) and subtracting baseline. Philippe Rocca-Serra peak height as signal intensity EU H2020 PhenoMenAl cosmos tracer based metabolomics working group maximum m/z values signal intensity with baseline substraction total volume of cell culture is a measurement data item which denotes the volume occupied by a cell culture Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group total volume of cell culture https://github.com/ISA-tools/isa-matrix-datapackages/tree/master/src/sirm_datapkg an isotopologue distribution matrix is an information object used in tracer based metabolomics experiments to report the amount of possible isotopologues (sets of isotopomers) derived from the tracer in a metabolic network. the matrix hold the mass isotopomer distributions (MIDs) of Elementary Metabolite Unit (EMU) which will be used as state variables. An EMU is defined as a distinct subset of a metabolite’s atoms. EMUs can exist in a variety of mass states depending on their isotopic compositions. An EMU in its lowest mass state is referred to as M+0, while an EMU that contains one additional atomic mass unit (e.g., due to the presence of a 13C atom in place of a 12C atom) is referred to as M+1, with higher mass states described accordingly. An MID is a vector that contains the fractional abundance of each mass state of an EMU. Philippe Rocca-Serra DOI 10.1002/bit.21632 An Elementary Metabolite Unit (EMU) BasedMethod of Isotopically Nonstationary Flux Analysis, Jamey D. Young, Jason L. Walther, Maciek R. Antoniewicz, Hyuntae Yoo,Gregory Stephanopoulos, Department of Chemical Engineering, Massachusetts Institute of Technology. http://onlinelibrary.wiley.com/doi/10.1002/bit.21632/epdf EU H2020 PhenoMenAl cosmos tracer based metabolomics working group isotopologue distribution matrix a metabolic flux rate matrix is an information content entity which is defined as a 2 dimensional table associating chemical species with uptake and excretion rate in the cell Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolic flux rate matrix 1 a stoichiometry matrix is an information content entity holding arrays of stoichiometric coefficients, each associated to a specific chemical reactions Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group stoichiometry matrix a CHEBI identifier for chemical or an HMDB identifier a centrally registered identifier to denote a metabolite chemical entity Philippe Rocca-Serra EU H2020 PhenoMenAl metabolite identifier a KEGG pathway identifier such as map00010 (http://www.genome.jp/dbget-bin/www_bget?map00010) a centrally registered identifier which denotes a pathway data item Philippe Rocca-Serra EU H2020 PhenoMenAl pathway identifier a uniprot identifier such P20248 (http://www.uniprot.org/uniprot/P20248) a centrally registered identifier to denote a molecular entity of the type Protein. Philippe Rocca-Serra EU H2020 PhenoMenAl protein identifier a reactome identifier such as R-HSA-174054 a centrally registered identifier which denotes a chemical reaction. Philippe Rocca-Serra EU H2020 PhenoMenAl reaction identifier calibration is a process which relies on comparison between measurements in order to estimate the reliability of the measurements performed on a particular device or instrument configuration. a calibration process may be used to identify a systematic error in measurement and possibly include it into an error model. a calibration process may be used to detect degradation of parts of instruments when long data acquisition times are needed (e.g. degradation of a chromatography column in a GC-MS chain). Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group calibration quality control is a process which aims to ensure that procedures for producing a material or a measurement remain within established error tolerance margins. Quality control often relies on the use of references or standards against which readings are gauged. those standards can be 'negative control' which should produce in an absence of signal or 'positive control', which should result in the presence of a signal of known quality and intensity. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group quality control assessing across studies variability is a quality control process which aims at monitoring the consistency of signal acquisitions between different studies (for instance in the context of meta-analysis and data integration) in order to detect unwanted causes of variation (i.e. variation that was not planned and that should be taken into account). Philippe Rocca-Serra EU H2020 PhenoMenAl assessing across studies variability assessing instrument conditionning is a quality control process which aims at monitoring the stability of the analytical instrument prior to running data acquisition on specimen of interest by running a set of control runs. Philippe Rocca-Serra EU H2020 PhenoMenAl assessing instrument conditioning assessing within study variability is a quality control process which aims at monitoring the consistency of signal acquisition throughout the course of a study in order to detect unwanted causes of variation (i.e. variation that was not planned and that should be taken into account). Philippe Rocca-Serra EU H2020 PhenoMenAl assessing within study variability assessing study batch-to-batch variation is a within study variably quality control which specifically looks at how batching of data acquisition contributes to adding unwanted noice and how to account for it. Philippe Rocca-Serra EU H2020 PhenoMenAl assessing study batch to batch variation detecting carry over event is a quality control process which aims to determine if measurements in one sample are affected to earlier measurements made on different samples and indicative of insufficient matrix regeneration between 2 data acquisition events. this is usually assessed by running solvent blanks or sample preparation blank between analytical runs. Philippe Rocca-Serra carry over detection EU H2020 PhenoMenAl detecting carry over event detecting departure from linearity event is a quality control process which aims to determine if measurements respond in a linear fashion of a linear increase of concentration of analytes. this is usually assessed by running a dilution series between analytical runs. Philippe Rocca-Serra linearity departure detection EU H2020 PhenoMenAl detecting departure from linearity event detecting sample degradation event is a quality control process which aims to determine if measurements in samples are affected by their run order or time of acquisition. This is usually assessed by running the same analytical samples at different points along the data acquistion plan (technical replication at the begining and end of runs). Philippe Rocca-Serra sample degradatation detection EU H2020 PhenoMenAl detecting sample degradation event an investigation which focused on measuring small biological molecules known as metabolite with the goal of understanding biochemical process underlying normal or pathological biological processes Philippe Rocca-Serra EU H2020 PhenoMenAl metabolomics investigation lipidomics investigation is an investigation which aims at determining the lipid content of a biological system under given experimental conditions using data acquisition techniques such as mass spectrometry, nmr spectroscopy or chromatography techniques. Philippe Rocca-Serra EU H2020 PhenoMenAl lipidomics investigation stable isotope resolved metabolomics study is a kind of investigation which uses non-radioactive isotope for labeling compounds which are precursors in key metabolic reaction. These studies therefore allow deciphering reaction and understanding the fluxes in cells. Tracer based pathway discovery study is a specific type of fluxomics study which aims at discovery new metabolic routes and their associated signature metabolites by using isotopically labeled tracers Philippe Rocca-Serra SIRMS tracer based metabolite profiling cosmos tracer based metabolomics working group stable isotope resolved metabolomics study A kind of assay which attempts to identify and measure relative concentration of all possible metabolites using the method high-performance liquid chromatography (HPLC; formerly referred to as high-pressure liquid chromatography), is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. Alejandra Gonzalez-Beltran Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group https://en.wikipedia.org/wiki/High-performance_liquid_chromatography metabolite quantitation using high performance liquid chromatography a kind of assay which attempts to identify and measure specific compound/ metabolites (known in advance) expressed as concentration or relative abundance ratio to a standard in a extract derived from a specimen using techniques such as gas chromatography mass spectrometry, liquid chromatography mass spectrometry, NMR spectroscopy or liquid chromatography DAD Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group targeted metabolite profiling a kind of assay which attempts to identify and measure relative concentration of all possible metabolites present in a extract derived from a specimen using techniques such as gas chromatography mass spectrometry, liquid chromatography mass spectrometry, NMR spectroscopy. Alejandra Gonzalez-Beltran Philippe Rocca-Serra global metabolite profiling EU H2020 PhenoMenAl cosmos tracer based metabolomics working group untargeted metabolite profiling a fresh culture medium is a culture medium which presents its nominal characteristisc in terms of molecular concentration of its components, pH, and physical chemical expected properties. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group fresh culture medium spent culture medium is a culture medium which has been added to a cell culture and which has been depleted of its component as used by the growing cell and which has received the by products of cell metabolites excreted by the cells. Therefore, spent culture medium will different significantly in pH and physical chemical properties from the initial fresh culture medium added to the cell as the begining of the cell culture. Spent culture medium is usually recovered by aspiration or mild centrifugation (as not to distrupt cell membrane) of the cell culture. Philippe Rocca-Serra cell culture supernatant spent medium EU H2020 PhenoMenAl cosmos tracer based metabolomics working group spent culture medium metabolism quenching is a planned processed whose objective is a quick extinction of all biochemical reactions occuring in a biological system in order to fix molecular entity concentrations for downstream quantitation and analysis. An array of physical or chemical agent may be used to achieve that goal. Philippe Rocca-Serra metabolism immediate extinction EU H2020 PhenoMenAl metabolism quenching direct metabolism quenching by solvent is a kind biochemical reaction extinction process which relies on organic solvents to denature enzymatic machinery and inactivate it. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group direct metabolism quenching by solvent a type of metabolism immediate extinction using cold acetonitrile Philippe Rocca-Serra metabolism quenching using QDA EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolism quenching by 13 CD3-QDA in cold CH3CN a type of metabolism extinction which uses refrigerated buffer containing 60% of methanol ammonium bicarbonate solution Philippe Rocca-Serra cooled 60% methanol NH4HCO3 metabolism quenching EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolism quenching using precooled 60 percent methanol ammonium bicarbonate buffer a type of metabolism extinction which uses refrigerated buffer containing 60% of methanol HEPES solution Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolism quenching using precooled 60 percent methanol HEPES buffer a type of metabolism extinction which uses refrigerated PBS buffer Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolism quenching using precooled PBS buffer acetonitrile 5%, isopropanol 95% for 15 minutes at flow rate 1 ml/min, an elution program is a set of recorded instructions which determine the mobile phase (gas or liquid) composition, pressure, temperature and flow rate during the chromatography separation. Philippe Rocca-Serra cosmos tracer based metabolomics working group elution program derivatization is a technique used in chemistry which transforms a chemical compound into a product (the reaction's derivate) of similar chemical structure, called a derivative. That compound has properties more amenable to a particular analytical method. Some samples analyzed by GC require derivatization in order to make them suitable for analysis. Compounds that have poor volatility, poor thermal stability, or that can be adsorbed in the injector will exhibit nonreproducible peak areas, heights, and shapes. Other compounds that respond poorly on a specific detector may need to be “tagged” with a different functional group to improve detection. Philippe Rocca-Serra EU H2020 PhenoMenAl adapted from https://en.wikipedia.org/wiki/Derivatization and https://www.restek.com/pdfs/CFTS1269.pdf. Last accessed: 2018-01-11 derivatization a kind of derivatization which results in the addition of acetyl group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Philippe Rocca-Serra EU H2020 PhenoMenAl EU cosmos tracer based metabolomics working group acetylation a kind of derivatization which results in the addition of trifluoroacetyl group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Alejandra Gonzalez-Beltran Philippe Rocca-Serra EU H2020 PhenoMenal trifluoroacetylation a kind of derivatization which results in the addition of alkyl group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Philippe Rocca-Serra EU H2020 PhenoMenal alkylation a kind of derivatization which results in the addition of methyl group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Philippe Rocca-Serra EU H2020 PhenoMenal methylation a kind of derivatization which results in the addition of oxime group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Philippe Rocca-Serra EU H2020 PhenoMenal oximation a kind of derivatization which results in the addition of silyl group to molecules in an attempt to make ions derived from it more volatile in a gas-chromatography experiment. Philippe Rocca-Serra EU H2020 PhenoMenal silylation Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific atoms by their isotope. Philippe Rocca-Serra https://en.wikipedia.org/wiki/Isotopic_labeling isotopic labeling Specific isotopic labeling refers to the placement of a single label (e.g., 2H, 13C, or 15N) in a specified location in a molecule. Philippe Rocca-Serra specific isotopic labeling EU H2020 PhenoMenAl http://www.sigmaaldrich.com/content/dam/sigma-aldrich/articles/stable-isotopes/biomolecular_nmr.pdf isotopic labeling with positional labeled tracer Uniform labeling refers to biosynthetic labeling of all carbon, nitrogen, or hydrogen sites with stable isotopes. Uniform labeling of proteins with 15N is particularly convenient because of the strategic locations of nitrogens in the backbone and the absence of homonuclear couplings due to the intervening carbons. It is also possible to replace all of the carbons with 13C, although in this case the spectroscopy has to deal with the network of couplings among bonded carbons. Similarly, all of the hydrogens can be replaced with deuterons in order to attenuate the dipolar couplings among the hydrogens that often present complications and difficulties in the experiments. Philippe Rocca-Serra EU H2020 PhenoMenAl http://www.sigmaaldrich.com/content/dam/sigma-aldrich/articles/stable-isotopes/biomolecular_nmr.pdf isotopic labeling with uniformly labeled tracer a process of collecting a sample when the cells of cell culture growth are collected at a specific phase of the cell division cycle (e.g collection at G2/G1). This often requires a cell synchronization step. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at cell cycle phase a process of collecting a sample when the cells of a cell culture growth are not dividing Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at cytostatic phase a process of collecting a sample when the cell culture growth can be approximated by a logarithm function. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at logarithmic phase collection at specific cell culture passage is a kind of specimen collection which occurs after a strictly defined number of cell culture splitting, defined to control how many cell divisions have been performed. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at specific cell culture passage collection at stabilization phase before experiment is a kind of specimen collection process which takes places once cells have reached a stationary growth phase and prior the main experimental intervention is applied. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at stabilization phase before experiment a process of collecting a sample when the cell culture growth has reached a plateau, indicative of a steady state Alejandra Gonzalez-Beltran Philippe Rocca-Serra collection at steady state phase EU H2020 PhenoMenAl cosmos tracer based metabolomics working group collection at stationary phase Flux balance analysis is a mathematical approach for analyzing the flow of metabolites through a metabolic network. Flux balance analysis calculates the flow of metabolites through a metabolic network, thereby making it possible to predict the growth rate of an organism or the rate of production of a biotechnologically important metabolite. Philippe Rocca-Serra What is flux balance analysis? Jeffrey D. Orth, Ines Thiele, and Bernhard Ø. Palsson Nat Biotechnol. 2010 Mar; 28(3): 245–248. doi: 10.1038/nbt.1614 cosmos tracer based metabolomics working group flux balance analysis Philippe Rocca-Serra cosmos tracer based metabolomics working group 13C-constrained flux balance analysis an isotopomer data matrix is a table resulting from the analysis of NMR data acquired in the context of tracer based studies and which contains information about chemical entity assignment Philippe Rocca-Serra MSIO isotopomer data matrix Correcting for the effects of natural abundance in stable isotope resolved metabolomics experiments involving ultra-high resolution mass spectrometry. BMC Bioinformatics. 2010 Mar 17;11:139. doi: 10.1186/1471-2105-11-139. natural abundance correction is a data transformation which aims to take into account the contribution of natural random variation in isotopic composition in the environment and adjust for it during the calculation of mass isotopologue distribution in a tracer based metabolomics experiment Hunter Moseley Philippe Rocca-Serra BMC Bioinformatics. 2010 Mar 17;11:139. doi: 10.1186/1471-2105-11-139. Correcting for the effects of natural abundance in stable isotope resolved metabolomics experiments involving ultra-high resolution mass spectrometry. cosmos tracer based metabolomics working group isotope natural abundance correction metabolic flux analysis is a type of investigation which uses data from tracer based studies to provide insights into cellular metabolites creation and destruction. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolic flux analysis steady-state 13C metabolic flux analysis is a metabolic flux analysis approach which relies on 13C tracer experiments and requires long incubation period necessary to meet methodological requirements that all reactions under study have reach steady state. By feeding cells a 13C-labeled substrate and subsequently measuring the patterns of isotope incorporation in downstream metabolic products, extensive information about the intracellular distribution of carbon flux can be obtained. This enables system-wide quantification of reversible, parallel, and cyclic metabolic pathways that would be otherwise unidentifiable based solely upon measurements of extracellular nutrient uptake and product excretion (Zamboni et al., 2009). While 13C MFA provides a rich source of phenotypic information, the application of this technique to mammalian systems presents unique challenges. In particular, the presence of subcellular compartmentation, complex media formulations, and slow labeling dynamics can lead to significant difficulties in experimental design and data interpretation (Zamboni, 2011). Philippe Rocca-Serra conventional 13C metabolic flux analysis conventional 13C-MFA EU H2020 PhenoMenAl cosmos tracer based metabolomics working group https://www.ncbi.nlm.nih.gov/pubmed/22140245 steady state 13C metabolic flux analysis Isotopically non-stationary MFA (INST-MFA) is a metabolic flux analysis which provides an approach to circumvent limitations from other methods through computational analysis of metabolite labeling patterns obtained during the transient labeling period prior to isotopic steady state (Wiechert and Noh, 2005). This approach offers several advantages over steady-state MFA, including shorter experimental times and the ability to determine fluxes with increased precision (Nöh and Wiechert, 2011; Young and Walther, 2008). Philippe Rocca-Serra INST-13C-MFA EU H2020 PhenoMenAl cosmos tracer based metabolomics working group https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535509/ isotopically non-stationary 13C-metabolic flux analysis a tracer analysis is a type of experimental procedure which relies on tracer molecules, usually non radioactive, to probe metabolic pathways and biochemical routes Philippe Rocca-Serra EU H2020 PhenoMenAl tracer analysis a normalization process which relies on the signal intensity measured for several reference compounds (internal standards) injected or added to the test samples in known quantities, thereby allowing sample comparison which have been placed on equal footing. Philippe Rocca-Serra cosmos tracer based metabolomics working group normalization by optimal selection with multiple internal standards a normalization process which relies on the computing to total signal intensity by simply summing up those signals and then for each sample measurements, dividing it by the total signal. The total sum is used as reference to which sample signals are then compared. Philippe Rocca-Serra cosmos tracer based metabolomics working group normalization to a total sum a normalization process used in mass spectrometry signal processing which takes into account the fact that analytes can interact with internal standards and impair accurate estimatation of these. The interaction phenomenon is known as cross contribution and needs to be compensated for. Philippe Rocca-Serra Compensation for Systematic Cross-Contribution Improves Normalization of Mass Spectrometry Based Metabolomics Data. Henning Redestig, Atsushi Fukushima, Hans Stenlund, Thomas Moritz, Masanori Arita, Kazuki Saito and Miyako Kusano. RIKEN Plant Science Center, Tsurumi-ku, Suehiro-cho, 1-7-22 Yokohama, Kanagawa, 230-0045, Japan, and Umea Plant Science Center, Umea University, 901 87 Umea, Sweden. Anal. Chem., 2009, 81 (19), pp 7974–7980 DOI: 10.1021/ac901143w cosmos tracer based metabolomics working group normalization to multiple standard with cross contribution compensation ruv_starter_analysis(Y,X,ctl) http://www-personal.umich.edu/~johanngb/ruv/howto/howto.html the 2 step normalization is a normalization process which uses 2 complementary steps provided suitable quality controls have been supplied. The process attempts to remove overall unwanted variation given suitable controls and uses factors of interest in the normalization. It relies on linear mixed effects model which utilizes quality control metabolites to obtain normalized data in typical metabolomics experiments. Philippe Rocca-Serra RUV RUV-2 Statistical Methods for Handling Unwanted Variation in Metabolomics Data. Alysha M. De Livera, Marko Sysi-Aho, Laurent Jacob, Johann A. Gagnon-Bartsch, Sandra Castillo, Julie A. Simpson, and Terence P. Speed Biostatistics Unit, Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, VIC 3800, Australia Zora Biosciences Oy, FIN-02150 Espoo, Finland VTT Technical Research Centre of Finland, P. O. Box 1000, FI-02044 VTT Espoo, Finland Laboratoire de Biométrie et Biologie Evolutive, Université Lyon 1, CNRS, INRA, UMR5558, Villeurbanne, France Department of Statistics, University of California, Berkeley, California United States, 94720 Bioinformatics Division, Walter and Eliza Hall Institute, 1 G Royal Parade, Parkville, Victoria 3052, Australia Department of Mathematics and Statistics, University of Melbourne, VIC 3800, Melbourne, Australia Anal. Chem., 2015, 87 (7), pp 3606–3615 DOI: 10.1021/ac502439y Using control genes to correct for unwanted variation in microarray data. Gagnon-Bartsch and Speed, 2012. Available at: http://biostatistics.oxfordjournals.org/content/13/3/539.full. Removing Unwanted Variation from High Dimensional Data with Negative Controls. GagnonBartsch, Jacob, and Speed, 2013. Available at: http://statistics.berkeley.edu/tech-reports/820. cosmos tracer based metabolomics working group http://www-personal.umich.edu/~johanngb/ruv/index.html remove unwanted variation 2-step normalization a normalization process which relies on the signal intensity measured for one reference compound (an internal standard) injected or added to the test samples in known quantity, thereby allowing sample comparison which have been placed on equal footing based on this reference. Philippe Rocca-Serra cosmos tracer based metabolomics working group normalization to a single internal standard ribose extraction metabolite extraction is an extraction process which aims to retrieve small molecules known as metabolites, from a specimen Philippe Rocca-Serra EU H2020 PhenoMenAl metabolite extraction lipid extraction is an extraction which aims to retrieve lipid (hydrophobic carbohydrate) from a specimen Philippe Rocca-Serra EU H2020 PhenoMenAl lipid extraction polar metabolite extraction is a metabolite extraction which aims to retrieve water soluble or metabolites with polar solvent solubility properties. This is usually exclusive of hydrophobique, lipophile and lipid like metabolites. Philippe Rocca-Serra EU H2020 PhenoMenAl polar metabolite extraction cell layer enzymatic digestion is a material component separation process which uses an enzyme, usually a protease, to lyse the bonds between cultured cells and their substrates (usually a microplate, which may be coated with anchoring material such as collagen). Once the digestion is complete, cell layers can be harvested with minimal damage to the cells themselves. Philippe Rocca-Serra cosmos tracer based metabolomics working group cell layer enzymatic digestion cell scraping is a material component separation technique which uses mechanism means (as opposed to enzymatic ones) to detach cultured cells from the growth substrate. The technique is thought to be more aggressive and cause cellular breakage but has the benefit of avoiding use of enzymes, which may have their own side effects on cellular content. Philippe Rocca-Serra cosmos tracer based metabolomics working group cell scraping centrifugation is a material component separation process which relies on centrifugational forces applied by means of high velocity rotation to a sample placed in a vial or tube in a rotor, fixed to an centrifugation instrument. Philippe Rocca-Serra EU H2020 PhenoMenAl centrifugation gas chromatography is a material component separation process which use a mobile phase in gaseous form to force a mixture of chemical through chromatography columns and associated detecting equipment, which may be a mass spectrometry in GC-MS applications. Philippe Rocca-Serra GC EU H2020 PhenoMenAl gas chromatography high performance liquid chromatography is a kind of material component separation process which uses a mobile phase in liquid form to force a mixture of chemical through chromatography columns and associated detecting equipment, which may be a mass spectrometry in LC-MS applications. the notion of high performance comes from the fact that higher pressure is applied to the liquid phase to pass material with adsorbant properties. Those may vary depending on the composition of the mobile phase (gradients between 2 solutions may be used). Philippe Rocca-Serra HPLC EU H2020 PhenoMenAl adapted from https://en.wikipedia.org/wiki/High-performance_liquid_chromatography high performance liquid chromatography biomass is a rate measurement datum of how much biochemical or biological material is produced over a period of time. it is usually reported in 'per hour'. Philippe Rocca-Serra COSMOS EU H2020 PhenoMenAl biomass Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the metabolic pathway's activity under different conditions. Flux is therefore of great interest in metabolic network modelling, where it is analysed via flux balance analysis. amount per unit of time maybe normalized by protein content Philippe Rocca-Serra metabolic rate http://en.wikipedia.org/wiki/Flux_%28metabolism%29 metabolic flux An extracellular flux is a metabolic flux indicating the rate of absortion or release of a molecular entity by a cell system from or to its surroundings, respectively. Philippe Rocca-Serra https://www.microbialcellfactories.com/content/13/1/152 EU H2020 PhenoMenAl cosmos tracer based metabolomics working group extracellular flux an excretion flux is a metabolic flux indicating the rate of release of a metabolite by a cell system to its surroundings. Alejandra Gonzalez-Beltran Philippe Rocca-Serra excretion rate EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolite excretion flux an uptake flux is a metabolic flux indicating the rate of absorption of a molecular entity by a cell system from its surroundings Philippe Rocca-Serra consumption rate uptake rate EU H2020 PhenoMenAl cosmos tracer based metabolomics working group metabolite uptake flux the reaction rate is a rate measurement datum denoting a biochemical reaction as measured according to standard experimental methods. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group reaction rate continuous fermentation cell culture is a type of processed material which involved a bacterial or yeast cell stock grown in conditions such as nutrients are added and product removed at a steady rate throughout the culture process. This is usually achieved using the specific type of fermenter known as a fed-batch culture reactor). classes could be moved to become subclasses of 'cell culture process' Philippe Rocca-Serra EU H2020 PhenoMenAl http://ib.bioninja.com.au/options/untitled/b1-microbiology-organisms/batch-versus-continuous.html continuous fermentation cell culture a cell culture population where cells are grown on top of each other, producing two layers of cells on the surface of the growth substrate, usually a flask or a petri dish classes could be moved to become subclasses of 'cell culture process' Philippe Rocca-Serra EU H2020 PhenoMenAl double layer cell culture a cell culture population where no cells are grown on top of each other, producing a single layer of cells on the surface of the growth substrate, usually a flask or a petri dish classes could be moved to become subclasses of 'cell culture process' Philippe Rocca-Serra EU H2020 PhenoMenAl monolayer cell culture https://www.ncbi.nlm.nih.gov/pubmed/20109035 a sandwich cell culture is a type of cell culture population where the grown cells are in contact with a substratum at the bottom and the top, thereby providing a more defined boundary and level of interaction than in suspension grown cells or in classic monolayer cell cultures. classes could be moved to become subclasses of 'cell culture process' Philippe Rocca-Serra EU H2020 PhenoMenAl sandwich cell culture a 3D cell culture is a cultured cell population grown in conditions which better mimicks in-vivo growth environment (i.e. more effectively than a 2D culture) allowing more complex recapitulation of cellular processes. These cell cultures are achieved by used of scaffolding agents. classes could be moved to become subclasses of 'cell culture process' Philippe Rocca-Serra spheroid culture EU H2020 PhenoMenAl https://www.thermofisher.com/blog/cellculture/3d-culturing-leads-parkinsons-breakthrough/ 3D cell culture A Chromatography column is a device used in chromatography for the separation of chemical compounds. A chromatography column contains the stationary phase, allowing the mobile phase to pass through it. Chromatography columns of different types are used in both gas and liquid chromatography. Alejandra Gonzalez-Beltran Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group https://en.wikipedia.org/wiki/Chromatography_column chromatography column Alejandra Gonzalez-Beltran Philippe Rocca-Serra An Instrument which is used to carry out a high performance liquid chromatography (HPLC; formerly referred to as high-pressure liquid chromatography) technique. HPLC is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material. The schematic of an HPLC instrument typically includes a degasser, sampler, pumps, and a detector. The sampler brings the sample mixture into the mobile phase stream which carries it into the column. The pumps deliver the desired flow and composition of the mobile phase through the column. The detector generates a signal proportional to the amount of sample component emerging from the column, hence allowing for quantitative analysis of the sample components. A digital microprocessor and user software control the HPLC instrument and provide data analysis. EU H2020 PhenoMenAl https://en.wikipedia.org/wiki/High-performance_liquid_chromatography HPLC instrument 96-well microplate is an array of wells usually arranged in 8 rows of 12 columns whose volume range from 0.2 ml to 1.5 ml and which are used to grow cell or perform biochemical, in-vitro reactions. The material making up the plate may vary and may be surface treated in many custom way. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group 96-well microplate a chemostat is a device to which fresh medium is continuously added, while culture liquid is continuously removed to keep the culture volume constant. By changing the rate with which medium is added to the bioreactor the growth rate of the microorganism can be easily controlled. It allows culture to reach physiological steady state and chemostat is often used to gather steady state data about an organism in order to generate a mathematical model relating to its metabolic processes. The name chemostat stems from "Chemical environment is static". The most striking advantages of chemostats are two-fold: microorganisms can be kept at a constant environmental conditions until the cultivated microorganisms reach steady state, defined by their specific growth rate (μ) being in balance with the dilution rate (D). Once the system is equilibrated, the steady state data can be used for quantification of physiological parameters and metabolic rates of organisms, which are eventually required for the parameterization of mathematical models. Philippe Rocca-Serra 10.4319/lom.2014.12.432 http://onlinelibrary.wiley.com/doi/10.4319/lom.2014.12.432/epdf EU H2020 PhenoMenAl cosmos tracer based metabolomics working group http://en.wikipedia.org/wiki/Chemostat chemostat a coated microplate is a kind of microplate whom surface has been treated in some, for instance by covalently attaching protein such as antibodies and cell matrix molecules to favor cell growth or induce speficic cellular behavior. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group coated microplate a constantly fed-btach culture reactor is a device in which the feed rate of a growth-limiting substrate is constant, i.e. the feed rate is invariant during the culture. Philippe Rocca-Serra CFBC EU H2020 PhenoMenAl cosmos tracer based metabolomics working group http://en.wikipedia.org/wiki/Fed-batch_culture#Constantly-fed-batch_culture http://onlinelibrary.wiley.com/doi/10.4319/lom.2014.12.432/epdf constantly fed-batch culture reactor an exponentially fed-batch culture reactor is a device which deliver the ability to grow cells in a way non too dissimilar to that of a chemostat based culture, meaning that the cells are in a quasi steady-state condition. Philippe Rocca-Serra EFBC EU H2020 PhenoMenAl cosmos tracer based metabolomics working group http://onlinelibrary.wiley.com/doi/10.4319/lom.2014.12.432/epdf exponentially fed-batch culture reactor A container in which fermentation takes place. Alejandra Gonzalez-Beltran Philippe Rocca-Serra COSMOS tracer based metabolomics working group EU H2020 PhenoMenAl fermenter a flask is a kind of container used for cell culture, and which is available in an array of material (usually transparent plastic polymer) which may be surface treated. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group flask a petri dish is a container used to grow cells or perform biochemical reactions, which used to be made of glass, but which is now available in a variety of surface treated or non-treated plastic polymers. a petri dish is a thin cylinder with the upper part acting as a lid, resting on small peg, large enough to enable gaseaous exchanges but still preventing water evaporation. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group petri dish a uncoated microplate is a kind of microplate whom surface has not received any treatment and is uniquely made of polymer. Philippe Rocca-Serra EU H2020 PhenoMenAl cosmos tracer based metabolomics working group uncoated microplate EU H2020 PhenoMenAl mass spectrometry instrument import from NMRMLCV NMR instrument high dose is a dose specifically set to trigger strong response in the system it is administered to, those effects may be toxic. Also, the denomination allows a discrete, categorical classification of the dose points, irrespective of the actual quantity administered thereby allowing to capture the intent of the operator, something which is not necessary explicit when reading the quantitative dose reading (specific to a chemical entity and a system). Philippe Rocca-Serra EU H2020 PhenoMenAl high dose low dose is a dose specifically set to trigger no or very limited response in the system it is administered to, those effects are not expected to be toxic. Also, the denomination allows a discrete, categorical classification of the dose points, irrespective of the actual quantity administered thereby allowing to capture the intent of the operator, something which is not necessary explicit when reading the quantitative dose reading (specific to a chemical entity and a system). Philippe Rocca-Serra EU H2020 PhenoMenAl low dose a "lethal dose" represents a dose (usually recorded as dose per kilogram of subject body weight) at which a given percentage of subjects will die. Philippe Rocca-Serra EU H2020 PhenoMenAl https://en.wikipedia.org/wiki/Lethal_dose lethal dose the "lethal dose 50" represents a dose (usually recorded as dose per kilogram of subject body weight) at which 50% of subjects will die. Alejandra Gonzalez-Beltran Philippe Rocca-Serra LD50 EU H2020 PhenoMenAl https://en.wikipedia.org/wiki/Lethal_dose lethal dose 50 medium dose is a dose specifically set to trigger limited but clear response in the system it is administered to, those effects are not expected to be toxic but may be. Also, the denomination allows a discrete, categorical classification of the dose points, irrespective of the actual quantity administered thereby allowing to capture the intent of the operator, something which is not necessary explicit when reading the quantitative dose reading (specific to a chemical entity and a system). Philippe Rocca-Serra EU H2020 PhenoMenAl medium dose noael dose is a dose defined as the highest experimental point that is without adverse effect. Alejandra Gonzalez-Beltran Philippe Rocca-Serra No Observed Adverse Effect Level dose https://en.wikipedia.org/wiki/No-observed-adverse-effect_level NOAEL dose continuous fermentation cell culture is a type of processed material which involved a bacterial or yeast cell stock grown in conditions such as nutrients are added at the begining of the culture process and products removed at the end. classes could be moved to become subclasses of 'cell culture process' Alejandra Gonzalez-Beltran Philippe Rocca-Serra EU H2020 PhenoMenAl batch cell culture fluxomics is a kind of investigation which aims at identifying, quantifying the fluxes of molecules in cellular systems and understanding the cellular metabolism. Philippe Rocca-Serra cosmos tracer based metabolomics working group fluxomics investigation mass isotopomer fractional abundance is a measurement data item corresponding to the following: the most abundant species is given the value 100 and all other species are normalized relative to 100 and expressed as percent relative abundance. fractional abundance of Mx=Ax= (abundance Mx) / ∑(i=0..n) abundance Mi, where Mx represents mass isotopomer Mx. Alejandra Gonzalez-Beltran Philippe Rocca-Serra mass isotopomer distribution https://www.ncbi.nlm.nih.gov/pubmed/10362629 mass isotopomer fractional abundance steady state labeling experiment is a material processing used in fluxomics studies where cells cultures are grown continuously in the presence of radiolabeled tracer compound throughout multiple platings. The redistribution of the label into metabolic intermediates and end-products is analysed when the system has reached an isotopic and metabolic steady state. Philippe Rocca-Serra EU H2020 PhenoMenAl steady state isotopic labeling experiment the m/z notation is used for the independent variable in a mass spectrum. The mass-to-charge ratio (m/Q) is a physical quantity that is most widely used in the electrodynamics of charged particles, e.g. in electron optics and ion optics. It appears in the scientific fields of electron microscopy, cathode ray tubes, accelerator physics, nuclear physics, Auger electron spectroscopy, cosmology and mass spectrometry. Philippe Rocca-Serra adapted from wikipedia: https://en.wikipedia.org/wiki/Mass-to-charge_ratio m over z a m over z ratio which underwent a correction data transformation to take into account variations caused by a specific aspects of the data acquisition process. Philippe Rocca-Serra MSIO corrected m/z a m over z ratio which underwent a correction data transformation that takes into account the signal obtained from a reference compound and its spectral characteristics. Philippe Rocca-Serra MSIO reference corrected m/z a m over z ratio which underwent a correction data transformation that takes into account the signal obtained from a reference compound, its spectral characteristics as well as the contributions caused by adducts generated during the ionization process. Philippe Rocca-Serra MSIO reference and adduct corrected m/z Retention time (RT) is a measure of the time taken for a solute to pass through a chromatography column. It is calculated as the time from injection to detection. Philippe Rocca-Serra https://www.chromatographytoday.com/news/autosamplers/36/breaking-news/understanding-the-difference-between-retention-time-and-relative-retention-time/31166 retention time The area of a peak is a kind of data derived from a spectrum which is proportional to the product of its height and its width of a spectrum peak, but the proportionality constant depends on the peak shape. Philippe Rocca-Serra adapted from: https://terpconnect.umd.edu/~toh/spectrum/Integration.html peak area a normalized corrected peak area is a type of peak area which is produced followed a normalization data transformation and correction in order to make spectra comparable. Philippe Rocca-Serra MSIO normalized corrected peak area Signal intensity of all m/z values after integrating the whole peak and subtracting baseline Philippe Rocca-Serra peak area as signal intensity EU H2020 PhenoMenAl cosmos tracer based metabolomics working group total m/z signal intensity integrating over the whole peak with baseline substraction chemical entity assignment is an annotation which uses spectral information to assign and identify and molecular entity/chemical compound. Various methods manual and computer assisted may be used. Philippe Rocca-Serra chemical entity assignment assignment by database search is a type of chemical entity assignment which relies on probing chemical electronic libraries and chemical databases to determine matching structure and thereby attempt to assign a chemical identity. Searches may rely on InChi string or keys for instance. Philippe Rocca-Serra MSIO assignment by database search chemical entity assignment by direct assignment to standards is a data transformation process which uses spectral information from a known compound (ie. the standard) to match the signature and affirm identity based on the spectral features found in the sample. Philippe Rocca-Serra MSIO direct assignment to standard chemical entity assignment by indirect assignment to standards is a data transformation process which uses spectral information from a known compound (ie. the standard) to infer chemical properties about another compound found in the sample. Philippe Rocca-Serra MSIO indirect assignment to standard A category denoting a rather broad domain or field of interest, study, application, work, data, or technology. Topics have no clearly defined borders between each other. topic:0003 Topic Philippe Rocca-Serra isotopomer analysis Philippe Rocca-Serra isotopologue distribution analysis metabolism quenching by snap freeing in liquid nitrogen is a kind biochemical reaction extinction process which relies on extremely low temperature afforded by nitrogen in liquid state to denature enzymatic machinery of live cells or live tissue and inactivate it. Philippe Rocca-Serra LN2 snap freezing EU H2020 PhenoMenAl metabolism quenching by snap freezing in liquid nitrogen a normalization process which relies on the computing to arithmetic mean signal intensity over all measurements (controls and samples) and then for each sample measurements, adjusting the signal with the mean (by substracting the mean, allowing to retain measurement unit, which is not the case with dividing with the mean). The arithmetic mean is used as reference to which sample signals are then compared. Philippe Rocca-Serra cosmos tracer based metabolomics working group normalization to the mean import from PATO example to be eventually removed The term was used in an attempt to structure part of the ontology but in retrospect failed to do a good job Person:Alan Ruttenberg failed exploratory term Class has all its metadata, but is either not guaranteed to be in its final location in the asserted IS_A hierarchy or refers to another class that is not complete. metadata complete term created to ease viewing/sort terms for development purpose, and will not be included in a release organizational term Class has undergone final review, is ready for use, and will be included in the next release. Any class lacking "ready_for_release" should be considered likely to change place in hierarchy, have its definition refined, or be obsoleted in the next release. Those classes deemed "ready_for_release" will also derived from a chain of ancestor classes that are also "ready_for_release." ready for release Class is being worked on; however, the metadata (including definition) are not complete or sufficiently clear to the branch editors. metadata incomplete Nothing done yet beyond assigning a unique class ID and proposing a preferred term. uncurated All definitions, placement in the asserted IS_A hierarchy and required minimal metadata are complete. The class is awaiting a final review by someone other than the term editor. pending final vetting Core is an instance of a grouping of terms from an ontology or ontologies. It is used by the ontology to identify main classes. PERSON: Alan Ruttenberg PERSON: Melanie Courtot core placeholder removed An editor note should explain what were the merged terms and the reason for the merge. terms merged This is to be used when the original term has been replaced by a term imported from an other ontology. An editor note should indicate what is the URI of the new term to use. term imported This is to be used when a term has been split in two or more new terms. An editor note should indicate the reason for the split and indicate the URIs of the new terms created. term split This is to be used if none of the existing instances cover the reason for obsolescence. An editor note should indicate this new reason. We expect to be able to mine these new reasons and add instances as required. other true Hard to give a definition for. Intuitively a "natural kind" rather than a collection of any old things, which a class is able to be, formally. At the meta level, universals are defined as positives, are disjoint with their siblings, have single asserted parents. Alan Ruttenberg A Formal Theory of Substances, Qualities, and Universals, http://ontology.buffalo.edu/bfo/SQU.pdf universal A defined class is a class that is defined by a set of logically necessary and sufficient conditions but is not a universal "definitions", in some readings, always are given by necessary and sufficient conditions. So one must be careful (and this is difficult sometimes) to distinguish between defined classes and universal. Alan Ruttenberg defined class A named class expression is a logical expression that is given a name. The name can be used in place of the expression. named class expressions are used in order to have more concise logical definition but their extensions may not be interesting classes on their own. In languages such as OWL, with no provisions for macros, these show up as actuall classes. Tools may with to not show them as such, and to replace uses of the macros with their expansions Alan Ruttenberg named class expression Terms with this status should eventually replaced with a term from another ontology. Alan Ruttenberg group:OBI to be replaced with external ontology term A term that is metadata complete, has been reviewed, and problems have been identified that require discussion before release. Such a term requires editor note(s) to identify the outstanding issues. Alan Ruttenberg group:OBI requires discussion Biocrates Life Sciences AG, a biotechnology company, develops and markets targeted metabolic phenotyping solutions that support the discovery and validation of biomarkers for complex multifactorial diseases in pre-clinical and clinical research. The company offers mass-spectrometry based reproducible and quantitative kits and services that analyze various endogenous metabolites; and tools for insight into pathways and metabolic signatures of diseases, such as cancer or neurodegenerative diseases. It also offers metabolic phenotyping, and biomarker discovery and development services. Alejandra Gonzalez-Beltran Philippe Rocca-Serra Biocrates Life Sciences AG https://www.bloomberg.com/research/stocks/private/snapshot.asp?privcapId=20741978 Biocrates AG Agilent Technologies is an American public research, development and manufacturing company established in 1999 as a spin-off from Hewlett-Packard. The resulting IPO of Agilent stock was the largest in the history of Silicon Valley at the time. The company provides analytical instruments, software, services and consumables for the entire laboratory workflow. Alejandra Gonzalez-Beltran Philippe Rocca-Serra Agilent https://en.wikipedia.org/wiki/Agilent_Technologies Agilent Technologies Bruker Corporation is a manufacturer of scientific instruments for molecular and materials research, as well as for industrial and applied analysis. It is headquartered in Billerica, Massachusetts and is the publicly traded parent company of Bruker Scientific Instruments (Bruker AXS, Bruker BioSpin, Bruker Daltonics and Bruker Optics) and Bruker Energy & Supercon Technologies (BEST) divisions. Bruker Bruker Corporation https://en.wikipedia.org/wiki/Bruker Bruker AG Thermo Fisher Scientific is an American multinational biotechnology product development company, created in 2006 by the merger of Thermo Electron and Fisher Scientific. Alejandra Gonzalez-Beltran Philippe Rocca-Serra https://en.wikipedia.org/wiki/Thermo_Fisher_Scientific Thermo Fisher Scientific SVN $Revision: 717 $ IAO Release 2015-02-23