Ryan C. Thompson, Ph.D. Contact Address: 8656 Via Mallorca Unit G La Jolla, CA 92037 Phone: (908) 922-7470 Email: rct@thompsonclan.org Website: https://github.com/DarwinAwardWinner Summary ========== * Accomplished, experienced computational biologist with deep knowledge of biology, mathematics, statistics, and programming. * 11 years of bioinformatics experience answering a wide range of complex biological questions through analysis of large NGS- and microarray-based whole transcriptome and epigenetic data sets. * Focus on sound statistical analysis, effective data visualization and communication, and making expert knowledge and successful analysis methods available as re-usable software tools. * Supportive team member and experienced mentor with a strong ability to help others connect biological, statistical, and computational understanding. Education ========== 2012—2019: Ph.D. in Bioinformatics, Skaggs Graduate School of Chemical and Biological Sciences The Scripps Research Institute, La Jolla, California Advisor: Andrew Su 2005—2009: B.S. in Biology with High Distinction; B.A. in Mathematics University of Virginia, Charlottesville, Virginia Advisor: Paul J. Rushton Research Experience ========== Salomon & Su Labs, The Scripps Research Institute ---------- La Jolla, CA; 2012—2019 Contact: Dr. Andrew Su, asu@scripps.edu * Created an open source, reproducible workflow to analyze a large multi-omics next-gen sequencing dataset of 220 RNA-seq and ChIP-seq samples to reveal coordinated changes in histone marks and gene expression during CD4 + T-cell activation as well as epigenetic convergence between naive and memory cells after activation [1,3,8]. * Significantly improved cross-validated performance of machine learning classifier for identifying biomarkers of transplant rejection by developing appropriate single-sample microarray normalization procedures [5], including training a custom set of frozen RMA normalization vectors. Classifier is currently being developed into a clinical test for transplant dysfunction. * Performed a comprehensive comparative evaluation of over 20 subtly different statistical models for differential methylation in Illumina 450k arrays, selecting a model that best explained the observed sources and trends of variation in the data, including cross-domain application of a method originally designed for RNA-seq data. * Evaluated and optimized cost and performance of custom protocol for RNA-seq of human and primate blood samples while minimizing nuisance globin reads. Increased yield of useful reads nearly 2-fold [7]. * Investigated effects of life-span-extending drug on worm gene expression over time revealing that the drug retards age-related “transcriptional drift”, preserving a youthful phenotype at the molecular level [4]. * Implemented a systems biology tool to analyze and efficiently present and summarize differential expression for multiple gene set & pathway methods run on multiple pathway databases, as well as differential expression of individual genes within each pathway. * Performed comparative analysis of multiple differential expression statistical models to define best practice for optimal sensitivity while maintaining false positive control. Presented on theoretical and practical similarities and differences between methods. * Taught basic RNA-seq theory and practical analysis for the graduate-level introductory bioinformatics course. * Adapted common normalization methods from RNA-seq to improve performance in analysis of RASL-seq experiments [10]. * Active member of the Bioconductor community since 2012 and contributing developer for several Bioconductor packages. * Mentored 3 coworkers from both biology and programming backgrounds in learning bioinformatics. Summer Internship, Informatics IT, Merck & Co. ---------- Boston, MA; 2011 Contact: Adnan Derti, adnan.derti@gmail.com * Built a transcriptome assembly and quantification pipeline using Cufflinks, including fully-automated cluster job control for high-throughput reproducible analysis, and presented a conceptual overview of Cufflinks' assembly and quantification algorithms to help the team understand Cufflinks. * Assisted in a molecular genetics study to evaluate peformance of two variant calling algorithms in detection of causal mutations in antibiotic-resistant bacterial genomes. Gaasterland Lab, UCSD Bioinformatcs ---------- La Jolla, CA; 2010 - 2012 Contact: Terry Gaasterland, gaasterland@ucsd.edu * Designed and implemented Deloxer, a critical software step in a new Illumina mate-pair sequencing protocol using Cre recombination. Deloxer is published and now in use in several labs around the world [6]. * Performed a molecular genetics study to find potential causal mutations for fatal iron overload disease in critically endangered black rhinoceros by de novo assembly of transcriptomes for black rhino and closely-related white rhino. Developed a custom pipeline to match up ortholog gene pairs, discover single-nucleotide differences between them, and functionally annotate these differences, and delivered a list of potential causal variants to collaborators for follow-up. * Helped design & implement a large-scale high-throughput exome sequencing pipeline for SNP discovery and functional annotation, including QC and validation of on-target coverage depth and reproducibility of coverage. * Created a fully-automated pipeline to produce quality-control metrics and plots for Illumina high-throughput sequencing data for early identification of failed runs or samples. * Investigated the binding motif specificity of ZASC1 transcription factor in mouse T-cells using Affymetrix expression microarrays in ZASC1 siRNA knockdown experiment. * Analyzed miRNA target predictions using GO & KEGG grouping to identify target pathways of autophagy-related miRNAs for biological validation. Timko Lab, U. of Virginia Biology ---------- Charlottesville, VA; 2007—2009 Advisor: Paul J. Rushton * Undergraduate thesis: Designed and implemented Contig Farmer, an algorithm for efficient selective contig assembly starting from “seed” sequences of interest, and used Contig Farmer to accelerate transcription factor gene discovery in cowpea and tobacco shotgun genomic sequence data [11]. * Investigated transcription factors mediating plant stress response using expression microarray time-course, and refined the custom microarray design using data from previous runs to identify and eliminate uninformative probes, yielding an improved design for future studies. * Acted as interpreter to explain complex biological concepts to programmers and explain complex computational problems to biologists. Skills ========== Computing Skills: R/BioConductor, Python, Perl, Lisp, Java, C#, C++; Git version control; Remote UNIX system administration & software compilation, computing cluster job management & parallel computation * Public code: https://github.com/DarwinAwardWinner * StackOverflow Profile: http://stackoverflow.com/users/125921 Statistics & Data Analysis: Multi-omics NGS & microarray analysis, multi-factor linear and generalized linear regression, experimental design and parametrization, empirical Bayesian methods, predictive modeling of clinical outcomes, machine learning classifier training & validation, survival analysis, data visualization & presentation, reproducible research practices Wet Lab: PCR, molecular cloning, recombinant protein purification, epitope mapping, site-directed mutagenesis, 2D gels, real-time PCR, and associated data analysis Languages: English: native speaker; German: written and spoken Other Work Experience ========== Computing Advisor & Help Desk, U. Va. IT Dept. ---------- Charlottesville, VA; 2005—2007 * Provided support via phone and on-site for students, faculty, and staff having problems with computers, phone system, network access, malware, hardware setup, and university web services * Tasks included support for university-provided software, virus removal, iPod recovery, printer setup and repair, diagnosis of hardware malfunctions, and data recovery from failing hard disks Summer Sailing Instructor, Raritan Yacht Club ---------- Perth Amboy, NJ; 2006—2009 * Instructed children ages 8-18 in sailing skills, safety, seamanship, knots, rigging & de-rigging boats, navigation, and racing strategy and technique, with an emphasis on building character and self-reliance * Ensured safety of students and staff by maintaining boats and equipment in good repair, by being vigilant to traffic and hazards on a busy waterway, and by communicating and coordinating efficiently with other staff * Helped organize, run, and referee several regattas per season for students from RYC and neighboring yacht clubs Awards & Honors ========== 2006—2009 Echols Scholar, University of Virginia 2006 Phi Eta Sigma National Honor Society 2006 National Society of Collegiate Scholars 2005 Edward J. Bloustein Disguingished Scholar 2005 National Merit Scholar Peer-reviewed Publications ========== [1] Sarah A. LaMere, Ryan C. Thompson, Xiangzhi Meng, H. Kiyomi Komori, Adam Mark, and Daniel R. Salomon. H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3. The Journal of Immunology, 199(9):3158–3175, November 2017. doi:10/gchc9x. [2] S. M. Kurian, E. Velazquez, R. Thompson, T. Whisenant, S. Rose, N. Riley, F. Harrison, T. Gelbart, J. J. Friedewald, J. Charette, S. Brietigam, J. Peysakhovich, M. R. First, M. M. Abecassis, and D. R. Salomon. Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform. American Journal of Transplantation, 17(8):2103–2116, August 2017. doi:10/gbp6vr. [3] S. A. LaMere, R. C. Thompson, H. K. Komori, A. Mark, and D. R. Salomon. Promoter H3K4 methylation dynamically reinforces activation-induced pathways in human CD4 T cells. Genes & Immunity, 17(5):283–297, July 2016. doi:10/f97x85. [4] Sunitha Rangaraju, Gregory M. Solis, Ryan C. Thompson, Rafael L. Gomez-Amaro, Leo Kurian, Sandra E. Encalada, Alexander B. Niculescu, Daniel R. Salomon, and Michael Petrascheck. Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality. eLife, 4(December2015):1–39, December 2015. doi:10/ggcxmg. [5] S M Kurian, a N Williams, T Gelbart, D Campbell, T S Mondala, S R Head, S Horvath, L Gaber, R Thompson, T Whisenant, W Lin, P Langfelder, E H Robison, R L Schaffer, J S Fisher, J Friedewald, S M Flechner, L K Chan, A C Wiseman, H Shidban, R Mendez, R Heilman, M M Abecassis, C L Marsh, and D R Salomon. Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling. American Journal of Transplantation, 14(5):1164–1172, May 2014. doi:10/f5xswg. [6] Filip Van Nieuwerburgh, Ryan C Thompson, Jessica Ledesma, Dieter Deforce, Terry Gaasterland, Phillip Ordoukhanian, and Steven R Head. Illumina mate-paired DNA sequencing-library preparation using Cre-Lox recombination. Nucleic acids research, 40(3):e24, February 2012. doi:10/fmzd3r. Other Works ========== [7] Ryan C. Thompson, Terri Gelbart, Steven R Head, Phillip Ordoukhanian, Courtney Mullen, Dongmei Han, Dora M Berman, Amelia Bartholomew, Norma S Kenyon, and Daniel R Salomon. Optimizing yield of deep RNA sequencing for gene expression profiling of peripheral blood samples from cynomolgus monkeys (Macaca fascicularis). (In preparation). Institution: The Scripps Research Institute, 2019. [8] Ryan C. Thompson, Sarah A. Lamere, and Daniel R. Salomon. Reproducible genome-wide epigenetic analysis of H3K4 and H3K27 methylation in naïve and memory CD4+ T-cell activation. (In preparation). Institution: The Scripps Research Institute, 2019. [9] Ryan C. Thompson. Bioinformatic Analysis of Complex , High-Throughput Genomic and Epigenomic Data in the Context of CD4+ T-Cell Differentiation and Diagnosis and Treatment of Transplant Rejection. PhD thesis, The Scripps Research Institute, 2019. [10] Erick R Scott, H Benjamin Larman, Ali Torkamani, Nicholas J Schork, Nathan Wineinger, Max Nanis, Ryan C. Thompson, Reza B. Beheshti Zavareh, Luke L Lairson, Peter G Schultz, and Andrew I. Su. RASLseqTools: Open- source methods for designing and analyzing RNA-mediated oligonucleotide Annealing, Selection, and, Ligation sequencing (RASL-seq) experiments. bioRxiv, 2016. doi:10/ggcxmn. [11] Ryan C. Thompson, Paul J. Rushton, Tom W. Laudeman, and Michael P. Timko. Contig Farmer : A tool for extracting maximal-length contiguous sequences from a database of short sequence reads (Undergraduate Thesis), June 2009. Institution: University of Virginia. http://darwinawardwinner.github.io/resume/examples/UVa/contigfarmer.pdf [12] Ryan C. Thompson. The Sources and Limits of Geometric Rigor from Euclid Through Descartes, May 2008. Institution: University of Virginia. http://darwinawardwinner.github.io/resume/examples/UVa/math-history-paper.pdf Presentations and Teaching ========== * May 8, 2018: Guest lecturer on RNA-Seq for Advanced Tools and Data Challenges in Bioinformatics course (Lecture & Lab). University of California, San Diego, CA * November 21, 2016: Advanced RNA-Seq Analysis. Schork Lab, J. Craig Venter Institute, La Jolla, CA * August 15, 2016: RNA-seq Analysis. Bristol-Myers Squibb, Hopewell, NJ * April 29, 2016: Lecturer on Introductory RNA-seq Analysis for Applied Bioinformatics and Computational Biology course. The Scripps Research Institute, La Jolla, CA * December 21, 2015: Advanced RNA-Seq Analysis. Bristol-Myers Squibb, Hopewell, NJ * November 13, 2015: Advanced RNA-Seq Analysis. The Scripps Research Institute, La Jolla, CA