MARÍA GUTIÉRREZ-ARCELUS 77 Avenue Louis Pasteur, Suite 255 Divisions of and Rheumatology Boston, MA, 02115, USA Department of Medicine +1 617 525 4056 Brigham and Women’s Hospital [email protected] Harvard Medical School, Broad Institute

EDUCATION

2009-2014 University of Geneva, Geneva, Switzerland PhD in Bioinformatics • Highest Mention “Très bien” • title: Mechanisms and Tissue Specificity of the Genetic and Epigenetic Variation in Gene Regulation • Advisor: Emmanouil T. Dermitzakis, PhD

2005-2009 National Autonomous University of Mexico (UNAM), Cuernavaca, Mexico Bachelor of in Genomic Sciences • Honorific Mention • Top 3 in class diplomas in four consecutive years • GPA 9.7/10

ACADEMIC APPOINTMENTS

July 2019 - Harvard Medical School, Brigham and Women’s Hospital, Boston, USA present Instructor of Medicine

May 2019 - Single Cell Core, Brigham and Women’s Hospital, Boston USA present Director of Computational

GRANTS/FELLOWSHIPS

2014 - 2015 Early Postdoc Mobility Fellowship Granted by: Swiss National Science Foundation $71,850 for 18 months

2009 - 2011 PhD Fellowship Granted by: National Center for Competence in Research, Swiss National Science Foundation 2 years of PhD student salary

RESEARCH EXPERIENCE

July 2014- Immunogenomics - Harvard Medical School, Brigham and Women’s Hospital: Boston, USA present Postdoctoral Research Fellow Mentored by Dr. Soumya Raychaudhuri • Applied machine learning tools to low-input and single-cell RNA-seq datasets to find new functional features of innate and adaptive human T cells • Developed a statistical modeling framework and used high-depth RNA-seq to identify dynamic allele-specific expression during T cell activation across the genome • Developed a new bioinformatics algorithm to robustly quantify expression in highly polymorphic HLA genes, revealing regulatory variant associated with autoimmunity

1 July 2010- Functional Population Genomics - University of Geneva: Geneva, Switzerland Feb 2014 Graduate Research Scientist Mentored by Dr. Emmanouil T Dermitzakis • Applied machine learning tools to integrate genetic variation, DNA methylation and transcriptome high-throughput large-scale datasets for the understanding of gene regulation in T cells, fibroblasts and B cell lines (LCLs) • Set up experimental technique to assess nascent transcriptomes in LCLs (GRO-seq)

May-July System Genetics in Flies - Ecole Politechnique Fédéral de Lausanne: Lausanne, 2010 Switzerland Rotation Student Mentored by Dr. Bart Deplancke • Developed bioinformatics algorithms to study structural variation and expression data

Feb-March The Mammalian Circadian Timing System - University of Geneva: Geneva, Switzerland 2010 Rotation Student Mentored by Dr. Ueli Schibler • Performed electrophoretic mobility shift assays to identify a circadian transcription factor

Oct 2009-Jan Functional Population Genomics - University of Geneva: Geneva, Switzerland 2010 Rotation Student Mentored by Dr. Emmanouil T Dermitzakis • Developed bioinformatics algorithms and applied statistical analysis to study genetic variation and gene expression data from the 1000 genomes project

Feb-June Structural Genomic Variation - Center for Genomic Sciences, UNAM: Cuernavaca, 2009 Mexico Undergraduate Research Scientist Mentored by Dr. Rafael Palacios • Developed bioinformatics algorithms and applied statistical analysis for genome sequencing data to characterize copy number variants and repeated sequences

Aug-Nov Population Genomics of Gene Expression - Welcome Trust Sanger Institute: Hinxton, UK 2008 Undergraduate Research Scientist Mentored by Dr. Emmanouil T Dermitzakis • Developed bioinformatics algorithms and applied statistical analysis for associations between genome-wide SNP and gene expression across populations and cell types

Summer Structural Variation in Primate Genomes - Harvard Medical School: Boston, USA 2007 Undergraduate Research Scientist Mentored by Dr. Charles Lee • Performed data analysis and experimental validations of copy number variants

2005-2007 Genomic Rearrangements - Center for Genomic Sciences, UNAM: Cuernavaca, Mexico Undergraduate Research Scientist Mentored by Dr. Rafael Palacios • Developed bioinformatics algorithms to support project research

2 INVITED TALKS AND LECTURES

2020 Joint Biology Consortium, Brigham and Women’s Hospital: Boston USA Invited Speaker for Seminar Series What inter-individual differences in T cell activation can tell us about autoimmune disease mechanisms 2019 Department of Immunology, Harvard Medical School: Boston USA Invited Speaker for Bioinformatics Seminar Series What transcriptomics can tell us about human adaptive and innate T cell function 2019 Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School: Boston USA Invited Speaker for Seminar Series What transcriptomics can tell us about human adaptive and innate T cell functions 2018 International Laboratory for Research, UNAM: Queretaro, Mexico Invited Speaker for Seminar Series Gene regulation and autoimmune disease 2017 Horizons in Genomic Sciences Meeting: Cancun, Mexico Invited Speaker Dynamic allelic expression in response to human T cell activation 2012 Center for Genomic Sciences, UNAM: Cuernavaca, Mexico Invited Lecture (by teleconference) Transcriptomics 2011 Center for Genomic Sciences, UNAM: Cuernavaca, Mexico Invited Lecture Transcriptomics

EDITORIAL ACTIVITY

Ad hoc eLife Reviewer Plos Genetics Reviews Rheumatology Scientific Reports Annals of the Rheumatic Diseases Clinical Immunology

PUBLICATIONS h-index: 19 citations: 4,396 ()

F indicates >100 citations, * indicates equal contribution

First-authored Gutierrez-Arcelus M*, Baglaenko Y*, Arora J, Hannes S, Luo Y, Amariuta T, Teslovich N, Research Rao DA, Ermann J, Jonsson AH, NHLBI Trans-Omics for Precision Medicine (TOPMed) Articles Consortium, Navarrete C, Rich SS, Taylor KD, Rotter JI, Gregersen PK, Esko T, Brenner MB, Raychaudhuri S. Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci. Nat Genet. 2020 Mar;52(3):247-253.

Gutierrez-Arcelus M, Teslovich N, Mola AR, Polidoro RB, Nathan A, Hannes S, Slowikowski K, Watts GFM, Korsunsky I, Brenner MB, Raychaudhuri S, Brenner PJ. Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions. Nat Commun. 2019 Feb 8;10(1):687

3 F Gutierrez-Arcelus M*, Ongen H*, Lappalainen T*, Montgomery SB*, Buil A, Yurovsky A, Bryois J, Giger T , Romano L, Planchon A, Falconnet E, Bielser D, Gagnebin M, Padioleau I, Borel C, Letourneau A, Makrythanasis P, Guipponi M, Gehrig C, Antonarakis SE, Dermitzakis ET. Tissue-specific effects of genetic and epigenetic variation on gene regulation and splicing. Plos Genet. 2015 Jan 29;11(1):e1004958

Popadin K*, Gutierrez-Arcelus M*, Dermitzakis ET, Antonarakis SE. Genetic and Epigenetic Regulation of Human lincRNA Gene Expression. Am J Hum Genet. 2013 Dec 5;93(6):1015-26

F Gutierrez-Arcelus M, Lappalainen T, Montgomery SB, Buil A, Ongen H, Yurovsky A, Bryois J, Giger T, Romano L, Planchon A, Falconnet E, Bielser D, Gagnebin M, Padioleau I, Borel C, Letourneau A, Makrythanasis P, Guipponi M, Gehrig C, Antonarakis SE, Dermitzakis ET. Passive and active DNA methylation and the interplay with genetic variation in gene regulation. eLife 2013;2:e00523 Research Highlight in Nature Review Genetics: http://www.nature.com/nrg/journal/v14/n8/full/nrg3535.html Research Highlight in Genome Biology: http://genomebiology.com/2013/14/7/126

Co-authored Luo Y, Suliman S, Asgari S, Amariuta T, Baglaenko Y, Martínez-Bonet M, Research Ishigaki K, Gutierrez-Arcelus M, Calderon R, Lecca L, León SR, Jimenez J, Yataco Articles R, Contreras C, Galea JT, Becerra M, Nejentsev S, Nigrovic PA, Moody DB, Murray MB, Raychaudhuri S. Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians. Nat Commun. 2019 Aug 21;10(1):3765

Zhang F*, Wei K*, Slowikowski K*, Fonseka CY*, Rao DA*, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd; Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium [which includes Gutierrez-Arcelus M], Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 May 6

Davenport EE, Amariuta T, Gutierrez-Arcelus M, Slowikowski K, Westra HJ, Luo Y, Shen C, Rao DA, Zhang Y, Pearson S, von Schack D, Beebe JS, Bing N, John S, Vincent MS, Zhang B, Raychaudhuri S. Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial. Genome Biol. 2018 Oct 19;19(1):168

Donlin LT, Rao DA, Wei K, Slowikowski K, McGeachy MJ, Turner JD, Meednu N, Mizoguchi F, Gutierrez-Arcelus M, Lieb DJ, Keegan J, Muskat K, Hillman J, Rozo C, Ricker E, Eisenhaure TM, Li S, Browne EP, Chicoine A, Sutherby D, Noma A; Accelerating Medicines Partnership RA/SLE Network, Nusbaum C, Kelly S, Pernis AB, Ivashkiv LB, Goodman SM, Robinson WH, Utz PJ, Lederer JA, Gravallese EM, Boyce BF, Hacohen N, Pitzalis C, Gregersen PK, Firestein GS, Raychaudhuri S, Moreland LW, Holers VM, Bykerk VP, Filer A, Boyle DL, Brenner MB, Anolik JH. Methods for high-dimensonal analysis of 4 cells dissociated from cryopreserved synovial tissue. Arthritis Res Ther. 2018 Jul 11;20(1):139

Gaspar L, Howald C, Popadin K, Maier B, Mauvoisin D, Moriggi E, Gutierrez-Arcelus M, Falconnet E, Borel C, Kunz D, Kramer A, Gachon F, Dermitzakis ET, Antonarakis SE, Brown SA. The genomic landscape of human cellular circadian variation points to a novel role for the signalosome. eLife. 2017 Sep 4; 6

F Baran Y, Subramaniam M, Biton A, Tukiainen T, Tsang EK, Rivas MA, Pirinen M, Gutierrez-Arcelus M, Smith KS, Kukurba KR, Zhang R, Eng C, Torgerson DG, Urbanek C; GTEx Consortium, Li JB, Rodriguez-Santana JR, Burchard EG, Seibold MA, MacArthur DG, Montgomery SB, Zaitlen NA, Lappalainen T. The landscape of genomic imprinting across diverse adult human tissues. Genome Res. 2015 Jul;25(7):927-36

Popadin KY, Gutierrez-Arcelus M, Lappalainen T, Buil A, Steinberg J, Nikolaev SI, Lukowski SW, Bazykin GA, Seplyarskiy VB, Ioannidis P, Zdobnov EM, Dermitzakis ET, Antonarakis SE. Gene age predicts the strength of purifying selection acting on gene expression variation in humans. Am J Hum Genet. 2014 Dec 4;95(6):660-74

Panousis NI, Gutierrez-Arcelus M, Dermitzakis ET, Lappalainen T. Allelic mapping bias in RNA-sequencing is not a major confounder in eQTL studies. Genome Biol. 2014 Sep 20;15(9):467

F Kilpinen H*, Waszak SM*, Gschwind AR, Raghav SK, Witwicki RM, Orioli A, Migliavacca E, Wiederkehr M, Gutierrez-Arcelus M, Panousis NI, Yurovsky A, Lappalainen T, Romano-Palumbo L, Planchon A, Bielser D, Bryois J, Padioleau I, Udin G, Thurnheer S, Hacker D, Core LJ, Lis JT, Hernandez N, Reymond A, Deplancke B, Dermitzakis ET. Coordinated effects of sequence variation on DNA binding, structure, and transcription. Science. 2013 Nov 8;342(6159):744-7

Dimas AS, Nica AC, Montgomery SB, Stranger BE, Raj T, Buil A, Giger T, Lappalainen T, Gutierrez-Arcelus M; MuTHER Consortium, McCarthy MI, Dermitzakis ET. Sex-biased genetic effects on gene regulation in humans. Genome Res. 2012 Dec;22(12):2368-75

F Stranger BE, Montgomery SB, Dimas AS, Parts L, Stegle O, Ingle CE, Sekowska M, Smith GD, Evans D, Gutierrez-Arcelus M, Price A, Raj T, Nisbett J, Nica AC, Beazley C, Durbin R, Deloukas P, Dermitzakis ET. Patterns of cis regulatory variation in diverse human populations. PLoS Genet. 2012 Apr;8(4):e1002639

Perry GH, Xue Y, Smith RS, Meyer WK, Calışkan M, Yanez-Cuna O, Lee AS, Gutiérrez-Arcelus M, Ober C, Hollox EJ, Tyler-Smith C, Lee C. Evolutionary genetics of the human Rh blood group system. Hum Genet. 2012 Jul;131(7):1205-16

Montgomery SB, Lappalainen T, Gutierrez-Arcelus M, Dermitzakis ET. Rare and common regulatory variation in population-scale sequenced human genomes. PLoS Genet. 2011 Jul;7(7):e1002144

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F Asher G, Reinke H, Altmeyer M, Gutierrez-Arcelus M, Hottiger MO, Schibler U. Poly(ADP-ribose) polymerase 1 participates in the phase entrainment of circadian clocks to feeding. Cell. 2010 Sep 17;142(6):943-53

F Yang TP, Beazley C, Montgomery SB, Dimas AS, Gutierrez-Arcelus M, Stranger BE, Deloukas P, Dermitzakis ET. Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics. 2010 Oct 1;26(19):2474-6

F Montgomery SB, Sammeth M, Gutierrez-Arcelus M, Lach RP, Ingle C, Nisbett J, Guigo R, Dermitzakis ET. Transcriptome genetics using second generation sequencing in a Caucasian population. Nature. 2010 Apr 1;464(7289):773-7

Zepeda-Mendoza CJ, Lemus T, Yáñez O, García D, Valle-García D, Meza-Sosa KF, Gutierrez-Arcelus M, Márquez-Ortiz Y, Domínguez-Vidaña R, Gonzaga-Jauregui C, Flores M, Palacios R. Identical repeated backbone of the human genome. BMC Genomics. 2010 Jan 23;11:60

F Dimas AS, Deutsch S, Stranger BE, Montgomery SB, Borel C, Attar-Cohen H, Ingle C, Beazley C, Gutierrez Arcelus M, Sekowska M, Gagnebin M, Nisbett J, Deloukas P, Dermitzakis ET, Antonarakis SE. Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 2009 Sep 4;325(5945):1246-50

F Lee AS, Gutierrez-Arcelus M, Perry GH, Vallender EJ, Johnson WE, Miller GM, Korbel JO, Lee C. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies. Hum Mol Genet. 2008 Apr 15;17(8):1127-36

Flores M, Morales L, Gonzaga-Jauregui C, Domínguez-Vidaña R, Zepeda C, Yañez O, Gutierrez M, Lemus T, Valle D, Avila MC, Blanco D, Medina-Ruiz S, Meza K, Ayala E, García D, Bustos P, González V, Girard L, Tusie-Luna T, Dávila G, Palacios R. Recurrent DNA inversion rearrangements in the human genome. Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6099-106

Reviews Gutierrez-Arcelus M, Rich SS, Raychaudhuri S. Autoimmune diseases - connecting risk alleles with molecular traits of the immune system. Nat Rev Genet. 2016 Mar;17(3):160- 74

Richard SS, Gutierrez-Arcelus M, Tran CW, Park S, Couter CJ, Lee C, Structural diversity of the human genome and disease susceptibility, ELS, John Wiley & Sons, July 2008

Thesis Gutierrez-Arcelus M. Mechanisms and tissue specificity of the genetic and epigenetic variation in gene regulation. Geneva (Switzerland): University of Geneva; 2014. Thesis No 4641

OTHER SCIENTIFIC ACTIVITIES

Abstract talks 2019 ENCODE Consortium Meeting, Potomac, USA 2018 Translational Systems Immunology Keystone Symposium, Snowbird, USA 2017 American Society of Human Genetics, Orlando, USA

6 2016 ENCODE Consortium Meeting, San Diego, USA 2013 Epigenetics Gordon Research Conference, Smithfield, USA 2012 1st Annual BLUEPRINT Consortium Meeting, Barcelona, Spain 2012 European Society of Human Genetics meeting, Nuremberg, Germany 2012 8th Annual Meeting NCCR Frontiers in Genetics, Saas Fe, Switzerland 2012 1st Annual Meeting iGE3 (Institute for Genetics and Genomics in Geneva), Yverdon-Les- Bains, Switzerland 2011 Leena Peltonen School of Human Genomics, Hinxton, UK

Posters 2019 Federation of Clinical Immunology Societies, Boston, USA 2018 American Society of Human Genetics, San Diego, USA 2017 American Society of Human Genetics, Orlando, USA 2016 American Society of Human Genetics, Vancouver, Canada 2015 American Society of Human Genetics, Baltimore, USA 2015 Immunogenomics, Huntsville, USA 2013 The Biology of Genomes, Cold Spring Harbor Laboratory, USA 2010 7th Annual Meeting NCCR Frontiers in Genetics, Saas Fe, Switzerland 2010 Quantitative Evolutionary and Comparative Genomics Workshop, Okinawa, Japan Teaching 2009 0.5-hr sessions per week for 16 weeks, Bachelor level, “Introduction to R” within “Statistics” course, UNAM, Cuernavaca, Mexico

Public engagement 2011-2012 Co-founder of More Science for Mexico non-profit association (https://www.masciencia.org/) 2012 Tour guide for kids/teenagers at Human Genome Exhibition, University of Geneva 2013 Tour guide for all ages at Diabetes Day, University of Geneva

TECHNICAL SKILLS

Bioinformatics • Programming languages: R, Perl, Bash • Statistical methods: linear mixed models, logistic regression, dimensionality reduction, unsupervised clustering, and other machine learning tools • Software: read aligners, SAMTools, BEDTools, PLINK, GATK, Picard tools, VCFtools, IGV, IMPUTE2, SHAPEIT, MACS, Clustal, LiftOver, and others • Integrative analyses of high-throughput large-scale data sets including from bulk RNA-seq, single-cell RNA-seq, SNP genotype and expression arrays, DNA methylation, ATAC-seq, Global Run-On sequencing, ChIP-seq, structural variants

Experimental • 2016: culture and subcellular fractionation of lymphoblastoid cell lines (for NET- seq) • 2010-2013: library preparation for Global Run-On sequencing (GRO-seq), lymphoblastoid cell line and fibroblast culture, DNA bisulfite conversion, EMSA • 2007: quantitative PCR, Fluorescence in situ hybridization (FISH), fiber-FISH

LEADERSHIP SKILLS AND LANGUAGES

Management • 2019-present: Director of Computational Biology at Single Cell Genomics Core, Brigham and Women’s Hospital. Managing two bioinformatics analysts, and coordinating with the experimental branch of the service core • 2010-present: managed teams of up to 8 main participants, including laboratory technicians, postdocs, PhD students and bioinformaticians 7 • 2010-present: managed interdisciplinary collaborations with immunologists, computer scientists, biologists, rheumatologists and geneticists • 2012: co-organized Second European Symposium More Science for Mexico, Switzerland • 2010: co-organized NCCR Frontiers in Genetics PhD students retreat, Switzerland

Mentoring • 2015-2018: co-mentored (with advisor) 3 PhD students, working directly with them for 3-4 months each • 2018-present: leader of “Integrative functional genomics” section of Raychaudhuri laboratory, co-mentoring 3 postdocs and 5 PhD students through biweekly lunches, bi-weekly meetings, and one-to-one meetings as needed • 2017-present: mentored 5 PhD students in the Harvard Graduate Women In Science and Engineering program through monthly lunches

Languages • Spanish (native speaker), English (fluent), French (fluent), Italian (beginner)

PROFESSIONAL SOCIETIES

2014- American Society of Human Genetics Member 2019- Federation of Clinical Immunology Societies Member 2019- Genetics Society of America Member 2020- Childhood Arthritis and Rheumatology Research Alliance Member

REFERENCES

Postdoctoral • Dr. Soumya Raychaudhuri, Brigham and Women’s Hospital, Harvard Medical advisor School, [email protected], tel: +1 617 525 4484

Postdoctoral • Dr. Patrick Brennan, Brigham and Women’s Hospital, Harvard Medical School, research [email protected], tel: +1 617-525-1016 collaborators • Dr. Michael Brenner, Brigham and Women’s Hospital, Harvard Medical School, [email protected], tel: +1 617 525 1000

PhD advisor • Dr. Emmanouil (Manolis) Dermitzakis, University of Geneva [email protected], tel: +41 22 379 55 51

PhD • Dr. Stylianos Antonarakis, University of Geneva collaborator [email protected], tel: +41 22 379 57 07

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