Research

Immunogenomics

Every individual harbours a vast and unique repertoire of immune receptors (T-cell receptors and B-cell receptors) which discriminate, at the molecular level, self from non-self. The structural diversity of the T-cell receptor (TCR) that is necessary for recognizing diverse antigens is generated mainly by stochastic shuffling of the large number of short DNA segments that comprise TCR genes. Although the central importance of T cells in adaptive immunity has been well established for decades, the actual number and diversity of T cells that exist in an individual (i.e. the T-cell repertoire), how this changes in response to immune challenge, and how it varies from one individual to the next has remained unknown, and subject to much speculation.

We applied deep sequencing to T-cell repertoire analysis to obtain a first glimpse of repertoire diversity at the ultimate resolution of individual clonotypes (Freeman et al., Genome Research 2009). Currently, we are using these methods to explore the role of T cells in cancer, and how to enhance the anti-cancer immune response. We are particularly focussed on developing new sequence and informatics based approaches to T cell antigen discovery and characterization.

Synthetic immunology

It has been recognized for nearly three decades that patients with tumors that are strongly infiltrated by T-cells, in particular cytotoxic T cells, have better outcomes. We use computational approaches and targeted immuno-assays in the lab to gain insights into the nature of the anti-cancer T cell response, and to determine how and why it varies among healthy individuals and among cancer patients. These studies inform our programs for pre-clinical and clinical development of genetically engineered T cell therapies, including Chimeric Antigen Receptor (CAR-T) and Recombinant T cell Receptor (rTCR) therapies for cancer.

We are particularly focussed on using rTCRs to target cancer hotspot mutations. These are mutations that are seen in certain cancers at high frequency, which is unusual because most cancer mutations are random. We are systematically assessing hotspot mutations for their immunogenicity using a combination of genomics, mass spectrometry, flow cytometry and cellular immunoassays. We are optimizing procedures of isolating, expanding, activating, and redelivering these mutation-reactive T cells as targeted immunotherapies.

Metagenomics

A substantial proportion (at least 15%) of the global cancer burden is attributable to known infectious agents, such as HPV, HBV and H. pylori. It is possible that infectious agents may have a still greater role in cancer etiology, but traditional methods for finding them have limited sensitivity. We find pathogens by their sequence signatures in human tissues, using genomic methods. Our application of these methods to colorectal carcinoma identified a strong link to the emerging pathogen Fusobacterium nucleatum (Castellarin et al., Genome Research 2011). Currently, as part of the Cancer Research UK OPTIMISTICC Grand Challenge program we are characterizing the host immune response to F. nucleatum and other oncomicrobes, to inform vaccine development.

People

Robert Holt

Principal Investigator

Affiliations

• Distinguished Scientist, BC Cancer Research Institute
• Co-director, UBC Advanced Therapeutics Manufacturing Facility
• Professor of Medical Genetics, University of British Columbia
• Professor of Molecular Biology & Biochemistry, Simon Fraser University
• Associate Scientist, Canada's Michael Smith Genome Sciences Centre
• Affiliated Investigator, Vancouver Coastal Health Research Institute

Education

• Ph.D. – Pharmacology, University of Alberta, 1998
• B.Sc. – Biology, University of British Columbia, 1992

• Ali Nejatie
• Cody Despins
• Eric Yung
• Fei Teng
• Govinda Sharma
• Lisa Dreolini
• Maria Burns
• Monica Kotkoff
• Nicholas Viegas
• Petra Jozsa
• Scott Brown
• Tracy Lee
• Vanessa Zhu

Eric Yung

Staff Scientist

Post Doc – Leukemia/Gene Therapy, Terry Fox Laboratories/BC Cancer Agency, 2014
Post Doc – Gene Therapy/Virology, Children's Hospital/Harvard University, 2004
Ph.D. – Molecular Genetics/Virology, Albert Einstein College of Medicine, 2003
B.Sc. – Biochemistry, University of British Columbia, 1993

✉eyung@bccrc.ca

Ali Nejatie

Staff Scientist

Antibody/Antigen Discovery & Assay Development

Research Associate – Antibody Discovery, Simon Fraser University, 2024-2026
Post Doc – Pharmacology/Therapeutics, McGill University, 2021-2024
Ph.D. – Chemistry, Simon Fraser University, 2020
M.Sc.. – Chemistry, University of Guelph, 2016
B.Sc. – Biological Chemistry, University of Guelph, 2013

✉anejatie@bccrc.ca

Lisa Dreolini

Research Assistant III

Assay and process development

M.Sc. (Genetics), Terry Fox Laboratory, University of British Columbia, 2005
B.Sc. (Microbiology and Immunology), University of British Columbia, 2002

✉ldreolini@bccrc.ca

Scott Brown

Research Associate · Clinical Informatics Analyst

Applying informatics and visualization methods to explore the data landscape

Ph.D. (Genome Science + Technology), University of British Columbia, 2019
B.Sc. (Molecular Biology & Biochemistry and Computer Science), Simon Fraser University, 2013

✉sbrown@bccrc.ca · 604-675-8000 x 7501

Cody Despins

Postdoctoral Fellow

Adaptive immune responses to GI oncomicrobes

Ph.D. (Molecular Biology and Biochemistry), Simon Fraser University, 2025
B.Sc. (Biochemistry), University of Victoria, 2017

✉cdespins@bccrc.ca

Tracy Lee

PhD Candidate

Developing vaccine candidates against GI oncomicrobes

Ph.D. (in progress) (IOP), University of British Columbia
B.Sc. Honours (Immunology and Infection, Certificate in Biomedical Research), University of Alberta, 2023

✉tralee@bccrc.ca

Maria Burns

Masters Student

Developing antibody 'kill switch' for CAR-T cell therapy

M.Sc. (in progress) (IOP), University of British Columbia
B.Sc. Honours (Biology), Mount Saint Vincent University, 2024

✉mburns@bccrc.ca

Nicholas Viegas

MD/PhD Student

Developing & evaluating vaccine candidates against GI oncomicrobes

B.Sc. Honours (Microbiology & Immunology), University of British Columbia, 2024

✉nviegas@bccrc.ca

Petra Jozsa

Honours Student

Defining immunodominant proteins and antibody targets of GI oncomicrobes

B.Sc. Honours (in progress) (Health Sciences, Molecular Biology & Biochemistry), Simon Fraser University

✉pjozsa@bccrc.ca

Govinda Sharma

Research Affiliate

Developing and applying advanced in vitro platform technologies for T cell antigen discovery

Ph.D. (Genome Science + Technology), University of British Columbia, 2019
B.Sc. (Molecular Biology & Biochemistry, minor: Chemistry), Simon Fraser University, 2010

Immfinity · LinkedIn · ResearchGate

✉gsharma@bcgsc.ca · 604-675-8000 x 7501

Fei Teng

Research Affiliate

Combining T cell biology and bioinformatic platform to advance immunotherapies

Ph.D. (Immunology), Peking University, 2012
B.Med. (MD equivalent), Peking University, 2007

Immfinity · LinkedIn

✉fteng@bcgsc.ca · 604-675-8000 x 7501

Monica Kotkoff

Projects Coordinator

✉mkotkoff@bccrc.ca

Vanessa Zhu

Admin Assistant

✉vzhu@bccrc.ca

Publications

1. Brown SD, Dreolini L, Minor A, Mozel M, Wong N, Mar S, Lieu A, Khan M, Carlson A, Hrynchak M, Holt RA, Missirlis PI. A de novo algorithm for allele reconstruction from Oxford nanopore amplicon reads, with application to CYP2D6. Bioinformatics. 2026 Aug;42(8):btag535. doi: 10.1093/bioinformatics/btag535 PMID: 42477877
2. Despins CA, Round J, Dreolini L, Lee TS, Brown SD, Holt RA. Self-Multimerization of mRNA LNP-Derived Antigen Improves Antibody Responses. Vaccines. 2026 Jan 12;14(1):80. doi: 10.3390/vaccines14010080 PMID: 41600996
3. Knoetze N, Yung E, Bayega A, Brown SD, Holt RA. Identification of novel DNA sequence motifs that mdule transcription in T cells. BMC genomics. 2026 Jan 9;27:154. doi: 10.1186/s12864-025-12425-9 PMID: 41514212
4. Sharma G, Round J, Teng F, Ali Z, May C, Yung E, Holt RA. A synthetic cytotoxic T cell platform for rapidly prototyping TCR function. NPJ Precision Oncology 2024 Aug 19;8(1):182 doi: 10.1038/s41698-024-00669-9. PMID: 39160299
5. Kekre N, Hay KA, Webb JR, Mallick R, Balasundaram M, Sigrist MK, Clement AM, Nielsen JS, Quizi J, Yung E, Brown SD, Dreolini L, Waller DD, Smazynski J, Gierc NS, Loveless BC, Clark K, Dyer T, Hogg R, McCormick L, Gignac M, Bell S, Chapman DM, Bond D, Yong S, Fung R, Lockyer HM, Hodgson V, Murphy C, Subramanian A, Wiebe E, Yoganathan P, Medynski L, Vaillan DC, Black A, McDiarmid S, Kennah M, Hamelin L, Song K, Narayanan S, Rodrigo JA, Dupont S, Hawrysh T, Presseau J, Thavorn K, Lalu MM, Fergusson DA, Bell JC, Atkins H, Nelson BH, Holt RA. CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies. Front Immunol. 2022 Dec 19;13:1074740. doi: 10.3389/fimmu.2022.1074740. PMID: 36601119
6. Holt RA. Oncomicrobial vaccines: The potential for a Fusobacterium nucleatum vaccine to improve colorectal cancer outcomes. Cell Host & Microbe 2023 Jan 11. doi: 10.1016/j.chom.2022.11.014. PMID: 36634619
7. Rive CM, Yung E, Dreolini L, Brown SD, May CG, Woodsworth DJ, Holt RA. Selective B cell depletion upon intravenous infusion of replication-incompetent anti-CD19 CAR lentivirus. Mol Ther Methods Clin Dev 2022 May 29;26:4-14. doi: 10.1016/j.omtm.2022.05.006. PMID: 35755944
8. Brown SD, Dreolini S, Balasundaram M, Holt RA. Complete sequence verification of plasmid DNA using the Oxford Nanopore Technologies' MinION device. BMC Bioinformatics. 2023 Mar 24. doi: 10.1186/s12859-023-05226-y. PMID: 36964503
9. Despins CA, Brown SD, Robinson AV, Mungall AJ, Allen-Vercoe E, Holt RA. Modulation of the host cell transcriptome and epigenome by Fusobacterium nucleatum. mBio. 2021 Oct 26. doi: 10.1128/mbio.02062-21. PMID: 34700376
10. Kidman J, Principe N, Watson M, Lassmann T, Holt RA, Nowak AK, Lesterhuis WJ, Lake RA, Chee J. Characteristics of TCR Repertoire Associated With Successful Immune Checkpoint Therapy Responses. Front Immunol. 2020 Oct 14;11:587014. doi: 10.3389/fimmu.2020.587014. PMID: 33163002; PMCID: PMC7591700
11. Khalife R, Montroy J, Grigor EJM, Fergusson DA, Atkins H, Seftel M, Presseau J, Thavorn K, Holt RA, Hay K, Lalu MM, Kekre N. Building Canadian capacity for CAR-T cells in relapsed/refractory acute lymphoblastic leukaemia: a retrospective cohort study. Br J Haematol. 2020 Jul 20. 191(1). doi: 10.1111/bjh.16940. PMID: 32688454
12. Rive CM, Yung E, Hughes CS, Brown SD, Sharma G, Dreolini L, Warren C, Karasinska JM, Loree JM, Yapp DT, Morin GB, Renouf DJ, Schaeffer DF, Turcotte S and Holt RA. Recombinant T cell receptors specific for HLA-A*02:01-restricted neoepitopes containing KRAS codon 12 hotspot mutations. BioRxiv. https://doi.org/10.1101/2020.06.15.149021
13. Cochrane K, Robinson AV, Holt RA, Allen-Vercoe E. A survey of Fusobacterium nucleatum genes modulated by host cell infection. Microbial Genomics. 2020 Feb;6(2):e000300. doi: 10.1099/mgen.0.000300. PMID: 31661053
14. Dreolini L, Cullen M, Yung E, Laird L, Webb JR, Nelson BH, Hay KA, Balasundaram M, Kekre N and Holt RA. A Rapid and Sensitive Nucleic Acid Amplification Technique for Mycoplasma Screening of Cell Therapy Products. Molecular Therapy - Methods & Clinical Development. 2020 Jan 30;17:393-399. doi: 10.1016/j.omtm.2020.01.009. eCollection 2020 Jun 12. PMID: 32128343; PMCID: PMC7044503
15. Sharma G, Rive C and Holt RA. Rapid selection and identification of functional CD8+ T-cell epitopes from large peptide coding libraries. Nature Communications. 2019;10:4553. doi: 10.1038/s41467-019-12444-7
16. Grigor EJM, Fergusson D, Kekre N, Montroy J, Atkins H, Seftel M, Daugaard M, Presseau J, Thavorn K, Hutton B, Holt RA, Lalu MM. Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis. Transfusion Medicine Reviews. 2019 Apr;33(2):98-110. doi: 10.1016/j.tmrv.2019.01.005. PMID: 30948292
17. Korecki AJ, Hickmott JW, Lam SL, Dreolini L, Mathelier A, Baker O, Kuehne C, Bonaguro RJ, Smith J, Tan CV, Zhou M, Goldowitz D, Deussing JM, Stewart AF, Wasserman WW, Holt RA, Simpson EM. Twenty-seven Tamoxifen-Inducible iCre-Driver Mouse Strains for Eye and Brain; Including Seventeen Carrying a New Inducible-First Constitutive-Ready Allele. Genetics. 2019 Apr;211(4):1155-1177. doi: 10.1534/genetics.119.301984. PMID: 30765420
18. Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, Funnell T, Little N, de Souza CPE, Laan S, LeDoux S, Cochrane DR, Lim JLP, Yang W, Roth A, Smith MA, Ho J, Tse K, Zeng T, Shlafman I, Mayo MR, Moore R, Failmezger H, Heindl A, Wang YK, Bashashati A, Grewal DS, Brown SD, Lai D, Wan ANC, Nielsen CB, Huebner C, Tessier-Cloutier B, Anglesio MS, Bouchard-Côté A, Yuan Y, Wasserman WW, Gilks CB, Karnezis AN, Aparicio S, McAlpine JN, Huntsman DG, Holt RA, Nelson BH, Shah SP. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell. 2018 Jun 14;173(7):1755-1769.e22. doi: 10.1016/j.cell.2018.03.073. PMID: 29754820
19. Brown SD, Holt RA. Neoantigen characteristics in the context of the complete predicted MHC class I self-immunopeptidome. Oncoimmunology 2018 Dec 22;8(3):1556080. doi: 10.1080/2162402X.2018.1556080
20. Sneddon S, Dick I, Lee G, Musk AWB, Patch A-M, Pearson JV, Waddel N, Allcock RJN, Holt RA, Robinson BWS, Creaney J. Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations. Lung Cancer 2018 May;119:64-70. doi: 10.1016/j.lungcan.2018.03.009
21. Thorsson V, Gibbs DL, Brown SD, … Holt RA, … Shmulevich I. The Immune Landscape of Cancer. Immunity 2018 Apr 17;48(4):812-830.e14. doi: 10.1016/j.immuni.2018.03.023
22. Woodsworth DJ, Dreolini L, Abraham L, Holt RA. Targeted cell-to-cell delivery of protein payloads via the granzyme-perforin pathway. Molecular Therapy-Methods & Clinical Development 2017 Oct 10;7:132-145. doi: 10.1016/j.omtm.2017.10.003
23. Martin SD, Wick DA, Nielsen JS, Little N, Holt RA, Nelson BH. A library-based screening method identifies neoantigen-reactive T cells in peripheral blood prior to relapse of ovarian cancer. OncoImmunology 2017 Sep 21;7(1):e1371895. doi: 10.1080/2162402X.2017.1371895
24. Holt RA. Interpreting the T-cell receptor repertoire. Nature Biotechnology 2017 Sep 11;35(9):829-830. doi: 10.1038/nbt.3957
25. Sneddon S, Patch AM, Dick IM, Kazakoff S, Pearson JV, Waddell N, Allcock RJN, Holt RA, Robinson BWS, Creaney J. Whole exome sequencing of an abestos-induced wild-type murine model of malignant mesothelioma. BMC Cancer 2017 Jun 2;17(1):396. doi: 10.1186/s12885-017-3382-6
26. Bouquet J, Gardy JL, Brown SD, Pfeil J, Miller RR, Morshed M, Avina-Zubieta A, Shojania K, McCabe M, Parker S, Uyaguari M, Federman S, Tang P, Steiner T, Otterstater M, Holt RA, Moore R, Chiu CY, Patrick DM. RNA-seq analysis of gene expression, viral pathogen, and B-cell/T-cell receptor signatures in complex chronic disease. Clinical Infectious Diseases 2017 Feb 15;64(4):476-481. doi: 10.1093/cid/ciw767
27. Holt RA, Cochrane K. Tumor potentiating mechanisms of Fusobacterium nucleatum, a multifaceted microbe. Gastroenterology 2017 Mar;152(4):694-696. doi: 10.1053/j.gastro.2017.01.024
28. Woodsworth DJ, Holt RA. Cell-based therapeutics: making a faustian pact with biology. Trends on Molecular Medicine 2017 Feb;23(2):104-115. doi: 10.1016/j.molmed.2016.12.004
29. Brown SD, Hapgood G, Steidl C, Weng AP, Savage KJ, Holt RA. Defining the clonality of peripheral T cell lymphomas using RNA-seq. Bioinformatics 2017 Apr 15;33(8):1111-1115. doi: 10.1093/bioinformatics/btw810
30. Martin SD, Brown SD, Wick DA, Nielsen JS, Kroeger DR, Twumasi-Boateng K, Holt RA, Nelson BH. Low mutation burden in ovarian cancer may limit the utility of neoantigen-targeted vaccines. PloS one. 2016 May 18;11(5):e0155189. doi: 10.1371/journal.pone.0155189
31. Brown SD, Raeburn LA, Holt RA. Profiling tissue-resident T cell repertoires by RNA sequencing. Genome Medicine. 2015 Nov 30;7:125. doi: 10.1186/s13073-015-0248-x
32. Holt RA. Immunogenomics: a foundation for intelligent immune design. Genome Medicine. 2015 Nov 19;7(1):116. doi: 10.1186/s13073-015-0247-y
33. The Cancer Genome Atlas Research Network. Genomic Classification of Cutaneous Melanoma. Cell. 2015 Jun 18;161(7):1681-96. doi: 10.1016/j.cell.2015.05.044
34. Gibb EA, Warren RL, Wilson GE, Brown SD, Robertson G, Morin GB and Holt RA. Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma. Genome Medicine. 2015 Mar 5;7(1):22. doi: 10.1186/s13073-015-0142-6
35. Sharma G and Holt RA. T-cell epitope discovery technologies. Human Immunology. 2014 Jun;75(6):514-519.
36. Brown SD, Warren RL, Gibb E, Martin SD, Nelson BH, Holt RA. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Research. 2014 May;24(5):743-50. doi: 10.1101/gr.165985.113
37. Wick D, Webb JR, Nielsen JS, Martin S, Kroeger DR, Milne K, Castellarin M, Twumasi-Boating K, Watson PH, Holt RA, Nelson BH. Surveillance of the tumor mutanome by T cells during progression from primary to recurrent ovarian cancer. Clinical Cancer Research. 2014 Mar 1;20(5):1125-34. doi: 10.1158/1078-0432.CCR-13-2147
38. Woodsworth DJ, Castellarin M, Holt RA. Sequence analysis of T-cell repertoires in health and disease. Genome Medicine. 2013 Oct 30;5(10):98. doi: 10.1186/gm502
39. Watson CT, Steinberg KM, Huddleston J, Sudmant P, Warren RL, Malig M, Schein J, Willsey JA, Joy JB, Scott JK, Graves, Wilson RK, Holt RA, Eichler EE, Breden F. Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. American Journal of Human Genetics. 2013 Apr 4;92(4):530-46. doi: 10.1016/j.ajhg.2013.03.004
40. Warren RL, Choe G, Freeman DJ, Castellarin M, Munro S, Moore R, Holt RA. Derivation of HLA types from shotgun sequence datasets. Genome Medicine. 2012 Dec 10;4(12):95. doi: 10.1186/gm396
41. Castellarin M, Milne K, Zeng T, Tse K, Mayo M, Zhao YJ, Webb JR, Watson PH, Nelson BH, Holt RA. Clonal evolution of high-grade serous ovarian carcinoma from primary to recurrent disease. Journal of Pathology. 2013 Mar;229(4):515-24. doi: 10.1002/path.4105
42. The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012 Jul 18;487(7407):330-7. doi: 10.1038/nature11252
43. Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, Barnes R, Watson P, Allen-Vercoe E, Moore RA, Holt RA. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Research. 2012 Feb;22(2):299-306. doi: 10.1101/gr.126516.111
44. Moore RA, Warren RL, Freeman JD, Gustavsen JA, Chenard C, Friedman JM, Suttle CA, Zhao Y, Holt RA. The sensitivity of massively parallel sequencing for detecting candidate infectious agents associated with human tissues. PLoS One. 2011;6(5):e19838. doi: 10.1371/journal.pone.0019838
45. Warren RL, Freeman JD, Zeng T, Choe G, Munro S, Moore R, Webb JR, Holt RA. Exhaustive T-cell repertoire sequencing of human peripheral blood samples reveals signatures of antigen selection and a directly measured repertoire size of at least 1 million clonotypes. Genome Research. 2011 May;21(5):790-7. doi: 10.1101/gr.115428.110
46. Gardy JL et al. Whole Genome Sequencing and Social Network Analysis of a Tuberculosis Outbreak. New England Journal of Medicine. 2011 Feb 24;364(8):730-9. doi: 10.1056/NEJMoa1003176
47. Jones SJM et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biology. 2010;11(8):R82. doi: 10.1186/gb-2010-11-8-r82
48. Mead CL, Kuzyk MA, Moradian A, Wilson GM, Holt RA, Morin GB. Cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin. Journal of Neurochemistry. 2010 Jun;113(6):1491-503. doi: 10.1111/j.1471-4159.2010.06690.x
49. Freeman JD, Warren RL, Webb JR, Nelson BH, Holt RA. Profiling the T-cell receptor beta-chain repertoire by massively parallel sequencing. Genome Research. 2009 Oct;19(10):1817-24. doi: 10.1101/gr.092924.109
50. Horspool DR, Coope RJ and Holt RA. Efficient assembly of very short oligonucleotides using T4 DNA Ligase. BMC Research Notes. 2010 Nov 9;3:291. doi: 10.1186/1756-0500-3-291
51. Holt RA et al. Rebuilding microbial genomes. Bioessays. 2007 Jun;29(6):580-90
52. Warren RL, Sutton GG, Jones SJM and Holt RA. Assembling millions of short DNA sequences using SSAKE. Bioinformatics. 2007 Feb 15;23(4):500-1
53. Wilson GE, Flibotte S, Missirlis PI, Marra MA, Jones S, Thornton K, Clark AG and Holt RA. Identification by full-coverage array CGH of human DNA copy number increases relative to chimpanzee and gorilla. Genome Research. 2006 Feb;16(2):173-81
54. Marra MA, Jones SJ, Astell CR, Holt RA et al. The Genome Sequence of the SARS-Associated Coronavirus. Science. 2003 May 30;300(5624):1399-404
55. Holt RA et al. The Genome Sequence of the Malaria Mosquito Anopheles gambiae. Science. 2002 Oct 4;298(5591):129-49
56. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA et al. The Sequence of the Human Genome. Science. 2001 Feb 16;291(5507):1304-51
57. Adams MD, Celniker SE, Holt RA et al. The Genome Sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185-95

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