• Wasserman, Wyeth

    Titles
    Executive Director and Scientist Level 3, CFRI

    Associate Dean, Research, CFRI, Faculty of Medicine, UBC
    Senior Scientist, Centre for Molecular Medicine and Therapeutics at CFRI
    Professor, Department of Medical Genetics, University of British Columbia

    Degrees / Designations
    B.Sc., PhD
    Primary Area of Research
    Evidence to Innovation
    Secondary Area(s) of Research
    Phone
    604-875-3812
    Fax
    604-875-3819
    Lab Phone
    604-875-3800
    Assistant
    Dora Pak (for lab research)
    Assistant Phone
    604-875-2000 ext. 5273
    Mailing Address

    Room 3109, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4

    Research Areas
    • Bioinformatics
    • Computational analysis of human genome sequence for the study of gene regulation and rare pediatric disorders
    • Comparative genome analysis
    Summary

    The Wasserman laboratory focuses on the creation, evaluation and application of computational methods for the analysis of genome sequences, with international strength in the study of cis-regulatory elements regulating gene expression. The lab creates widely used software and databases, performs applied analyses of genome sequences, and partners with diverse research teams on projects at the intersection of the computational and life sciences.

    Genome Sequencing has disrupted health research. The lab has been developing computational methods and tools to allow researchers and clinicians to identify functional consequences of genetic variations within cis-regulatory elements such as transcription factor binding sites. The 1500 transcription factors (TFs) within the human genome perform a key role in determining the set of active genes within a specific cell, as well as the magnitude of activity. Defects within TFs are widely recognized to contribute to genetic disorders - such changes may block the formation of certain cell types. Alterations in the DNA sequences bound by these factors can contribute causally to phenotypes, but much work remains to develop the essential computational detection methods.

    The lab studies gene regulation via multiple lines. First, the lab creates novel algorithms and software to predict interactions between TFs and DNA. The software incorporates diverse types of data to maximize prediction quality. Second, the lab collaborates internationally on the analysis of emerging data, such as an international FANTOM project to map regulatory sequence positions through the study of the 5’ end of RNA transcripts. Third, the lab engages in the applied analysis of genomes for pediatric disorders, in part to improve the delivery of information to clinicians. Such work is key to translating basic research advances into clinical impacts.

    Current Projects

    Our computational biology research is focused on genome analysis, with an emphasis on the identification and characterization of regulatory sequences controlling the transcription of genes. Cells respond to diverse stimuli by altering gene activity. Subtle alterations of the regulatory network can produce dramatic phenotypic consequences. Past and ongoing projects are linked to the central goals of understanding how genes are regulated and learning how to apply this knowledge to advance biomedical research. You can learn about many of our projects via our group homepage at www.cisreg.ca

    Identification and Analysis of Sequences Regulating Transcription
    Regulatory sequence analysis is complicated by a signal-to-noise problem. Transcription is regulated at one level by proteins that bind to short segments of DNA. These transcription factors activate or suppress gene activity by modulating the recruitment of RNA polymerase enzymes to the beginning of genes. As the target sequences for transcription factors are short, and transcription factors are tolerant of considerable variation in the sequences to which they bind, it is extremely difficult to distinguish functional binding sites in the vastness of the human genome. Using high-throughput ChIP-Seq and chromatin property data, we are developing a new generation of bioinformatics methods for the identification of regulatory sequences. Our work is increasingly focused on coupling the regulatory region discrimination with the interpretation of mutations detected by whole genome sequencing.

    Applied Bioinformatics
    At the CMMT we maintain a strong link between research and application. We work closely with our collaborators to impact human health. At present we are engineering regulatory sequences to direct gene expression selectively to target cells and tissues in the CanEuCre/Pleiades Promoter Project. With partners at BC Children’s Hospital, we are developing methods for efficient analysis of exome and genome sequences for children with genetic disorders.

    Selected Publications

    Review (Invited) Mathelier A, Shi W, Wasserman WW. Identification of altered cis-regulatory elements in human disease. Trends Genet. 31(2):67-76. (2015) PMID 25637093.

    Janer A, van Karnebeek CD, Sasarman F, Antonicka H, Al Ghamdi M, Shyr C, Dunbar M, Stockler-Ispiroglu S, Ross CJ, Vallance H, Dionne J, Wasserman WW, Shoubridge EA. RMND1 deficiency associated with neonatal lactic acidosis, infantile onset renal failure, deafness, and multiorgan involvement. Eur. J. Hum. Genet. (2015) PMID 25604853.

    Shyr C, Tarailo-Graovac M, Gottlieb M, Lee J, van Karnebeek C, Wasserman WW. FLAGS, frequently mutated genes in public exomes. BMC Med Genomics 7(1):64. (2014) PMID 25466818.

    Salvarinova R, Ye CX, Rossi A, Biancheri R, Roland EH, Pavlidis P, Ross CJ, Tarailo-Graovac M, Wasserman WW, van Karnebeek CD. Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. Neurogenetics (2014) PMID 25432320.

    Stockler S, Corvera S, Lambright D, Fogarty K, Nosova E, Leonard D, Steinfeld R, Ackerley C, Shyr C, Au N, Selby K, van Allen M, Vallance H, Wevers R, Watkins D, Rosenblatt D, Ross CJ, Conibear E, Wasserman W, van Karnebeek C. Single point mutation in Rabenosyn-5 in a female with intractable seizures and evidence of defective endocytotic trafficking. Orphanet J Rare Dis 9(1):141. (2014) PMID 25233840.

    Worsley Hunt R, Wasserman WW. Non-targeted transcription factors motifs are a systemic component of ChIP-seq datasets. Genome Biol. 15(7):412. (2014) PMID 25070602.

    Armstrong L, Biancheri R, Shyr C, Rossi A, Sinclair G, Ross CJ, Tarailo-Graovac M, Wasserman WW, van Karnebeek CD. AIMP1 deficiency presents as a cortical neurodegenerative disease with infantile onset. Neurogenetics 15(3):157-9. (2014) PMID 24958424.

    Worsley Hunt R, Mathelier A, Del Peso L, Wasserman WW. Improving analysis of transcription factor binding sites within ChIP-Seq data based on topological motif enrichment. BMC Genomics 15:472. (2014) PMID 24927817.

    Chen CY, Chang IS, Hsiung CA, Wasserman WW. On the identification of potential regulatory variants within genome wide association candidate SNP sets. BMC Med Genomics 7:34. (2014) PMID 24920305.

    Shyr C, Kushniruk A, Wasserman WW. Usability study of clinical exome analysis software: top lessons learned and recommendations. J Biomed Inform 51:129-36. (2014) PMID 24860971.

    de Leeuw CN, Dyka FM, Boye SL, Laprise S, Zhou M, Chou AY, Borretta L, McInerny SC, Banks KG, Portales-Casamar E, Swanson MI, D'Souza CA, Boye SE, Jones SJ, Holt RA, Goldowitz D, Hauswirth WW, Wasserman WW, Simpson EM. Targeted CNS Delivery Using Human MiniPromoters and Demonstrated Compatibility with Adeno-Associated Viral Vectors. Mol Ther Methods Clin Dev 1:5. (2014) PMID 24761428.

    FANTOM Consortium and the RIKEN PMI and CLST (DGT). (Mathelier/Wasserman are authors and members of the FANTOM Consortium). A promoter-level mammalian expression atlas. Nature 507(7493):462-70. (2014) PMID 24670764.

    Review Ye XC, Pegado V, Patel MS, Wasserman WW. Strabismus genetics across a spectrum of eye misalignment disorders. Clin. Genet. (2014) PMID 24579652.

    van Karnebeek CD, Sly WS, Ross CJ, Salvarinova R, Yaplito-Lee J, Santra S, Shyr C, Horvath GA, Eydoux P, Lehman AM, Bernard V, Newlove T, Ukpeh H, Chakrapani A, Preece MA, Ball S, Pitt J, Vallance HD, Coulter-Mackie M, Nguyen H, Zhang LH, Bhavsar AP, Sinclair G, Waheed A, Wasserman WW, Stockler-Ipsiroglu S. Mitochondrial carbonic anhydrase VA deficiency resulting from CA5A alterations presents with hyperammonemia in early childhood. Am. J. Hum. Genet. 94(3):453-61. (2014) PMID 24530203.

    Vilariño-Güell C, Rajput A, Milnerwood AJ, Shah B, Szu-Tu C, Trinh J, Yu I, Encarnacion M, Munsie LN, Tapia L, Gustavsson EK, Chou P, Tatarnikov I, Evans DM, Pishotta FT, Volta M, Beccano-Kelly D, Thompson C, Lin MK, Sherman HE, Han HJ, Guenther BL, Wasserman WW, Bernard V, Ross CJ, Appel-Cresswell S, Stoessl AJ, Robinson CA, Dickson DW, Ross OA, Wszolek ZK, Aasly JO, Wu RM, Hentati F, Gibson RA, McPherson PS, Girard M, Rajput M, Rajput AH, Farrer MJ. DNAJC13 mutations in Parkinson disease. Hum. Mol. Genet. 23(7):1794-801. (2014) PMID 24218364.

    Yang L, Zhou T, Dror I, Mathelier A, Wasserman WW, Gordân R, Rohs R. TFBSshape: a motif database for DNA shape features of transcription factor binding sites. Nucleic Acids Res. 42(Database issue):D148-55. (2014) PMID 24214955.

    Mathelier A, Zhao X, Zhang AW, Parcy F, Worsley-Hunt R, Arenillas DJ, Buchman S, Chen CY, Chou A, Ienasescu H, Lim J, Shyr C, Tan G, Zhou M, Lenhard B, Sandelin A, Wasserman WW. JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles. Nucleic Acids Res. 42(Database issue):D142-7. (2014) PMID 24194598.

    Cotton AM, Chen CY, Lam LL, Wasserman WW, Kobor MS, Brown CJ. Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains. Hum. Mol. Genet. 23(5):1211-23. (2014) PMID 24158853.

    Filges I, Nosova E, Bruder E, Tercanli S, Townsend K, Gibson W, Röthlisberger B, Heinimann K, Hall J, Gregory-Evans C, Wasserman W, Miny P, Friedman J. Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype. Clin. Genet. 86(3):220-228. (2014) PMID 24128419.

    Aminkeng F, Ross CJ, Rassekh SR, Brunham LR, Sistonen J, Dube MP, Ibrahim M, Nyambo TB, Omar SA, Froment A, Bodo JM, Tishkoff S, Carleton BC, Hayden MR, . Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent. Pharmacogenomics J. 14(2):160-70. (2014) PMID 23588107.

    Schmouth JF, Castellarin M, Laprise S, Banks KG, Bonaguro RJ, McInerny SC, Borretta L, Amirabbasi M, Korecki AJ, Portales-Casamar E, Wilson G, Dreolini L, Jones SJ, Wasserman WW, Goldowitz D, Holt RA, Simpson EM. Non-coding-regulatory regions of human brain genes delineated by bacterial artificial chromosome knock-in mice. BMC Biol. 11:106. (2013) PMID 24124870.

    Mathelier A, Wasserman WW. The next generation of transcription factor binding site prediction. PLoS Comput. Biol. 9(9):e1003214. (2013) PMID 24039567.

    Ye XC, Ng I, Seid-Karbasi P, Imam T, Lee CE, Chen SY, Herman A, Sharma B, Johal G, Gu B, Wasserman WW. Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers. JMIR Res Protoc 2(2):e25. (2013) PMID 23920006.

    Cheung WA, Ouellette BF, Wasserman WW. Compensating for literature annotation bias when predicting novel drug-disease relationships through Medical Subject Heading Over-representation Profile (MeSHOP) similarity. BMC Med Genomics 6 Suppl 2:S3. (2013) PMID 23819887.

    Robillard JM, Whiteley L, Johnson TW, Lim J, Wasserman WW, Illes J. Utilizing social media to study information-seeking and ethical issues in gene therapy. J. Med. Internet Res. 15(3):e44. (2013) PMID 23470490.

    Visscher H, Ross CJ, Rassekh SR, Sandor GS, Caron HN, van Dalen EC, Kremer LC, van der Pal HJ, Rogers PC, Rieder MJ, Carleton BC, Hayden MR, . Validation of variants in SLC28A3 and UGT1A6 as genetic markers predictive of anthracycline-induced cardiotoxicity in children. Pediatr Blood Cancer 60(8):1375-81. (2013) PMID 23441093.

    Cheung WA, Francis Ouellette B, Wasserman WW. Inferring novel gene-disease associations using Medical Subject Heading Over-representation Profiles. Genome Med 4(9):75. (2012) PMID 23021552.

    Cheung WA, Ouellette BF, Wasserman WW. Quantitative biomedical annotation using medical subject heading over-representation profiles (MeSHOPs). BMC Bioinformatics 13:249. (2012) PMID 23017167.

    Kwon AT, Arenillas DJ, Worsley Hunt R, Wasserman WW. oPOSSUM-3: advanced analysis of regulatory motif over-representation across genes or ChIP-Seq datasets. G3 (Bethesda) 2(9):987-1002. (2012) PMID 22973536.

    Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486(7403):395-9. (2012) PMID 22495314.

    Yusuf D, Butland SL, Swanson MI, Bolotin E, Ticoll A, Cheung WA, Zhang XY, Dickman CT, Fulton DL, Lim JS, Schnabl JM, Ramos OH, Vasseur-Cognet M, de Leeuw CN, Simpson EM, Ryffel GU, Lam EW, Kist R, Wilson MS, Marco-Ferreres R, Brosens JJ, Beccari LL, Bovolenta P, Benayoun BA, Monteiro LJ, Schwenen HD, Grontved L, Wederell E, Mandrup S, Veitia RA, Chakravarthy H, Hoodless PA, Mancarelli MM, Torbett BE, Banham AH, Reddy SP, Cullum RL, Liedtke M, Tschan MP, Vaz M, Rizzino A, Zannini M, Frietze S, Farnham PJ, Eijkelenboom A, Brown PJ, Laperrière D, Leprince D, de Cristofaro T, Prince KL, Putker M, del Peso L, Camenisch G, Wenger RH, Mikula M, Rozendaal M, Mader S, Ostrowski J, Rhodes SJ, Van Rechem C, Boulay G, Olechnowicz SW, Breslin MB, Lan MS, Nanan KK, Wegner M, Hou J, Mullen RD, Colvin SC, Noy PJ, Webb CF, Witek ME, Ferrell S, Daniel JM, Park J, Waldman SA, Peet DJ, Taggart M, Jayaraman PS, Karrich JJ, Blom B, Vesuna F, O'Geen H, Sun Y, Gronostajski RM, Woodcroft MW, Hough MR, Chen E, Europe-Finner GN, Karolczak-Bayatti M, Bailey J, Hankinson O, Raman V, LeBrun DP, Biswal S, Harvey CJ, DeBruyne JP, Hogenesch JB, Hevner RF, Héligon C, Luo XM, Blank MC, Millen KJ, Sharlin DS, Forrest D, Dahlman-Wright K, Zhao C, Mishima Y, Sinha S, Chakrabarti R, Portales-Casamar E, Sladek FM, Bradley PH, Wasserman WW. The transcription factor encyclopedia. Genome Biol. 13(3):R24. (2012) PMID 22458515.

    Schmouth JF, Banks KG, Mathelier A, Gregory-Evans CY, Castellarin M, Holt RA, Gregory-Evans K, Wasserman WW, Simpson EM. Retina Restored and Brain Abnormalities Ameliorated by Single-Copy Knock-In of Human NR2E1 in Null Mice. Mol. Cell. Biol. 32(7):1296-311. (2012) PMID 22290436.

    Kwon AT, Chou AY, Arenillas DJ, Wasserman WW. Validation of skeletal muscle cis-regulatory module predictions reveals nucleotide composition bias in functional enhancers. PLoS Comput. Biol. 7(12):e1002256. (2011) PMID 22144875.

    Worsley-Hunt R, Bernard V, Wasserman WW. Identification of cis-regulatory sequence variations in individual genome sequences. Genome Med 3(10):65. (2011) PMID 21989199.

    Vilariño-Güell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, Wszolek ZK, Vingerhoets F, Farrer MJ. VPS35 mutations in Parkinson disease. Am. J. Hum. Genet. 89(1):162-7. (2011) PMID 21763482.

    Fulton DL, Denarier E, Friedman HC, Wasserman WW, Peterson AC. Towards resolving the transcription factor network controlling myelin gene expression. Nucleic Acids Res. 39(18):7974-91. (2011) PMID 21729871.

    Portales-Casamar E, Evans A, Wasserman W, Pavlidis P. The NeuroDevNet Neuroinformatics Core. Semin Pediatr Neurol 18(1):17-20. (2011) PMID 21575836.

    Le Béchec A, Portales-Casamar E, Vetter G, Moes M, Zindy PJ, Saumet A, Arenillas D, Theillet C, Wasserman WW, Lecellier CH, Friederich E. MIR@NT@N: a framework integrating transcription factors, microRNAs and their targets to identify sub-network motifs in a meta-regulation network model. BMC Bioinformatics 12:67. (2011) PMID 21375730.

    Portales-Casamar E, Swanson DJ, Liu L, de Leeuw CN, Banks KG, Ho Sui SJ, Fulton DL, Ali J, Amirabbasi M, Arenillas DJ, Babyak N, Black SF, Bonaguro RJ, Brauer E, Candido TR, Castellarin M, Chen J, Chen Y, Cheng JC, Chopra V, Docking TR, Dreolini L, D'Souza CA, Flynn EK, Glenn R, Hatakka K, Hearty TG, Imanian B, Jiang S, Khorasan-zadeh S, Komljenovic I, Laprise S, Liao NY, Lim JS, Lithwick S, Liu F, Liu J, Lu M, McConechy M, McLeod AJ, Milisavljevic M, Mis J, O'Connor K, Palma B, Palmquist DL, Schmouth JF, Swanson MI, Tam B, Ticoll A, Turner JL, Varhol R, Vermeulen J, Watkins RF, Wilson G, Wong BK, Wong SH, Wong TY, Yang GS, Ypsilanti AR, Jones SJ, Holt RA, Goldowitz D, Wasserman WW, Simpson EM. A regulatory toolbox of MiniPromoters to drive selective expression in the brain. Proc. Natl. Acad. Sci. U.S.A. 107(38):16589-94. (2010) PMID 20807748.

    Ross CJ, Visscher H, Sistonen J, Brunham LR, Pussegoda K, Loo TT, Rieder MJ, Koren G, Carleton BC, Hayden MR,CPNDS Consortium. The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology. Thyroid 20(7):681-7. (2010) PMID 20578893.

    Malhotra D, Portales-Casamar E, Singh A, Srivastava S, Arenillas D, Happel C, Shyr C, Wakabayashi N, Kensler TW, Wasserman WW, Biswal S. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res. 38(17):5718-34. (2010) PMID 20460467.

    Milisavljevic M, Hearty T, Wong TY, Portales-Casamar E, Simpson EM, Wasserman WW. Laboratory Animal Management Assistant (LAMA): a LIMS for active research colonies. Mamm. Genome 21(5-6):224-30. (2010) PMID 20411264.

    Portales-Casamar E, Thongjuea S, Kwon AT, Arenillas D, Zhao X, Valen E, Yusuf D, Lenhard B, Wasserman WW, Sandelin A. JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res. 38 (Database issue):D105-10. (2010) PMID 19906716.

    Grants

    Genome Canada Computational Biology Grant, 2013-2016.  

    UBC Teaching and Learning Enhancement Fund, 2012-2015.

    NSERC Discovery Grant, 2010 – 2016.

    NIH NIGMS R01 Software Improvement Grant, 2010-2013.

    CIHR Operating Grant, 2007-2012.

    Canucks for Kids Catalyst Diabetes Research Fund, 2009-2010.

    CIHR Operating Grant, 2003-2006.

    CMMT-Merck Research Fund, 2002-2006.

    BC’s Children’s Hospital Foundation Start-up Fund, 2002-2006.

    Michael Smith Foundation for Health Research Establishment Award, 2004-2007.

    Canada Foundation for Innovation (CFI), B.C. Knowledge Development Fund, and IBM Canada, New Opportunity Funding, 2004-2005.

    Honours & Awards

    UBC Killam Teaching Prize, 2013.

    Basic Science Teaching Award, Department of Medical Genetics, University of British Columbia, 2011.

    New Investigator Award, Canadian Institutes of Health Research (CIHR),  2004-2009.

    Career Investigator Award, Michael Smith Foundation for Health Research (MSFHR), 2004-2009.

    Cremer Scholar, University of Wisconsin School of Medicine, 1992-1996.

    Wisconsin Alumni Research Foundation Fellow, 1991-1992.

    Paul Fowler Scholar, Washington State Legislature, 1987-1991.

    Washington Scholar, Washington State Legislature, 1987-1991.

    National Merit Scholar, National Merit Program, 1987-1988.

    Robert Byrd Scholar, United States Senate, 1987-1988.

    Seattle 's Young Achiever of the Year / American Academy of Achievement Honoree, 1987.

    Valedictorian, James A. Garfield High School, Seattle, Washington, 1987.

    Research Group Members
    Dave Arenillas, Bioinformatics Software Developer
    Julie Chih-yu Chen, PhD Student
    Alice Kaye, PhD Student
    Jessica JY Lee, Graduate Student
    Dr. Yifeng Li, Postdoctoral Research Fellow
    Dr. Anthony Mathelier, Deputy Group Leader
    Dora Pak, Research Manager 
    Wenqiang Shi, PhD Student
    Casper Shyr, PhD Student
    Dr. Maja Tarailo-Graovac, Research Associate
    Cynthia Xin Ye, Graduate and Medical School Student
    Allen Zhang, MD PhD Student