Tyra Wolfsberg, Ph.D.
Bioinformatics and Scientific Programming Core
A.B., Princeton University
Ph.D., University of California, San Francisco
Biography
Dr. Wolfsberg is the associate director of NHGRI's Bioinformatics and Scientific Programming Core. Her research program focuses on developing methodologies to integrate sequence, annotation and experimentally generated data so that bench biologists can quickly and easily obtain results for their large-scale experiments. She has collaborated with NHGRI investigators on a variety of projects, from genomic characterizations of DNAse I hypersensitive sites and retroviral integration sites to the annotation of the genome of the ctenophore Mnemiopsis leidyi.
Dr. Wolfsberg received her B.A. in molecular biology from Princeton University, followed by a Ph.D. in biochemistry and biophysics from the University of California, San Francisco. Dr. Wolfsberg made her transition to computationally based research by performing her postdoctoral fellowship at the National Center for Biotechnology Information (NCBI) at NIH. She worked as a staff scientist at NCBI before joining the NHGRI faculty in 2000.
Dr. Wolfsberg maintains a longstanding commitment to bioinformatics education and outreach. She is the co-chair the NIH lecture series Current Topics in Genome Analysis. The lectures, through their availability online, have reached over half a million viewers to date. She teaches in several bioinformatics courses offered to NHGRI staff and serves as a faculty member in bioinformatics at the annual AACR Workshop Molecular Biology in Clinical Oncology. In addition, she has authored a chapter on genomic databases for two editions of the textbook Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, and a chapter on the NCBI MapViewer for Current Protocols in Bioinformatics and Current Protocols in Human Genetics.
Dr. Wolfsberg has also served as a member of the Wellcome Trust-NIH Ph.D. Studentship Programme Advisory Committee (part of NIH's Graduate Partnerships Program) and is currently a member of the Wellcome Trust Ph.D. Programme Competition Committee, which evaluates doctoral programs funded by the Trust.
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Biography
Dr. Wolfsberg is the associate director of NHGRI's Bioinformatics and Scientific Programming Core. Her research program focuses on developing methodologies to integrate sequence, annotation and experimentally generated data so that bench biologists can quickly and easily obtain results for their large-scale experiments. She has collaborated with NHGRI investigators on a variety of projects, from genomic characterizations of DNAse I hypersensitive sites and retroviral integration sites to the annotation of the genome of the ctenophore Mnemiopsis leidyi.
Dr. Wolfsberg received her B.A. in molecular biology from Princeton University, followed by a Ph.D. in biochemistry and biophysics from the University of California, San Francisco. Dr. Wolfsberg made her transition to computationally based research by performing her postdoctoral fellowship at the National Center for Biotechnology Information (NCBI) at NIH. She worked as a staff scientist at NCBI before joining the NHGRI faculty in 2000.
Dr. Wolfsberg maintains a longstanding commitment to bioinformatics education and outreach. She is the co-chair the NIH lecture series Current Topics in Genome Analysis. The lectures, through their availability online, have reached over half a million viewers to date. She teaches in several bioinformatics courses offered to NHGRI staff and serves as a faculty member in bioinformatics at the annual AACR Workshop Molecular Biology in Clinical Oncology. In addition, she has authored a chapter on genomic databases for two editions of the textbook Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins, and a chapter on the NCBI MapViewer for Current Protocols in Bioinformatics and Current Protocols in Human Genetics.
Dr. Wolfsberg has also served as a member of the Wellcome Trust-NIH Ph.D. Studentship Programme Advisory Committee (part of NIH's Graduate Partnerships Program) and is currently a member of the Wellcome Trust Ph.D. Programme Competition Committee, which evaluates doctoral programs funded by the Trust.
Scientific Summary
As the associate director of NHGRI's Bioinformatics and Scientific Programming Core, Dr. Wolfsberg focuses on developing methodologies to integrate sequence, annotation and experimentally generated data so that bench biologists can quickly and easily obtain and interpret results from their large-scale experiments. When feasible, her group develops generalized solutions that can be applied to a variety of projects.
Dr. Wolfsberg played a leadership role in annotating the Mnemiopsis leidyi genome, the first fully sequenced genome of a ctenophore species. A major focus of this effort was to predict the locations of protein-coding genes using various types of biological sequence data. Her group also implemented a web-based genome browser to view the Mnemiopsis genome assembly, gene predictions and other biologically relevant sequence data. The computational pipelines will be used to annotate additional genomes in the future, and her group has already begun efforts to use these methodologies in the context of the Hydractinia genome project. Her analysis of the Mnemiopsis genome helped to demonstrate that ctenophores, which possess complex cell types such as neurons and muscle cells, are our oldest animal relatives; she anticipates that the work on Hydractinia will have an impact on our understanding of tissue regeneration, allorecognition and stem cell biology.
Dr. Wolfsberg's group has also developed analysis pipelines to align experimentally generated sequences to a genome and then compare the positions of interest to the coordinates of features displayed in a genome browser, such as genes and transcription start sites. They originally developed these annotation programs to characterize DNAse I hypersensitive sites, but later used this approach to characterize the sites at which different types of retroviruses integrate into mammalian genomes. This work has been used to assess the efficacy and safety of retroviruses used as vectors in gene therapy studies. More recently, her group has expanded the pipeline so it can process thousand of sequences at once (using so-called "next-generation" sequence data). One application of this enhancement has been to map retroviral integrations that are being used to inactivate every gene in the zebrafish genome, with the eventual goal of characterizing the resulting phenotypes.
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Scientific Summary
As the associate director of NHGRI's Bioinformatics and Scientific Programming Core, Dr. Wolfsberg focuses on developing methodologies to integrate sequence, annotation and experimentally generated data so that bench biologists can quickly and easily obtain and interpret results from their large-scale experiments. When feasible, her group develops generalized solutions that can be applied to a variety of projects.
Dr. Wolfsberg played a leadership role in annotating the Mnemiopsis leidyi genome, the first fully sequenced genome of a ctenophore species. A major focus of this effort was to predict the locations of protein-coding genes using various types of biological sequence data. Her group also implemented a web-based genome browser to view the Mnemiopsis genome assembly, gene predictions and other biologically relevant sequence data. The computational pipelines will be used to annotate additional genomes in the future, and her group has already begun efforts to use these methodologies in the context of the Hydractinia genome project. Her analysis of the Mnemiopsis genome helped to demonstrate that ctenophores, which possess complex cell types such as neurons and muscle cells, are our oldest animal relatives; she anticipates that the work on Hydractinia will have an impact on our understanding of tissue regeneration, allorecognition and stem cell biology.
Dr. Wolfsberg's group has also developed analysis pipelines to align experimentally generated sequences to a genome and then compare the positions of interest to the coordinates of features displayed in a genome browser, such as genes and transcription start sites. They originally developed these annotation programs to characterize DNAse I hypersensitive sites, but later used this approach to characterize the sites at which different types of retroviruses integrate into mammalian genomes. This work has been used to assess the efficacy and safety of retroviruses used as vectors in gene therapy studies. More recently, her group has expanded the pipeline so it can process thousand of sequences at once (using so-called "next-generation" sequence data). One application of this enhancement has been to map retroviral integrations that are being used to inactivate every gene in the zebrafish genome, with the eventual goal of characterizing the resulting phenotypes.
Publications
Rudd ML, Mohamed H, Price JC, O'Hara AJ, Le Gallo M, Urick ME; NISC Comparative Sequencing Program, Cruz P, Zhang S, Hansen NF, Godwin AK, Sgroi DC, Wolfsberg TG, Mullikin JC, Merino MJ, Bell DW. Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1. BMC Cancer, 14:884. 2014. [PubMed]
Renaud G, LaFave MC, Liang J, Wolfsberg TG, Burgess SM. trieFinder: an efficient program for annotating Digital Gene Expression (DGE) tags. BMC Bioinformatics, 15:329. 2014. [PubMed]
Moreland RT, Nguyen AD, Ryan JF, Schnitzler CE, Koch BJ, Siewert K, Wolfsberg TG, Baxevanis AD. A customized Web portal for the genome of the ctenophore Mnemiopsis leidyi. BMC Genomics, 15(1):316. 2014. [PubMed]
Lafave MC, Varshney GK, Gildea DE, Wolfsberg TG, Baxevanis AD, Burgess SM. MLV integration site selection is driven by strong enhancers and active promoters. Nucleic Acids Res, 42(7):4257-69. 2014. [PubMed]
Ryan JF, Pang K, Schnitzler CE, Nguyen AD, Moreland RT, Simmons DK, Koch BJ, Francis WR, Havlak P; NISC Comparative Sequencing Program, Smith SA, Putnam NH, Haddock SH, Dunn CW, Wolfsberg TG, Mullikin JC, Martindale MQ, Baxevanis AD. The genome of the ctenophore Mnemiopsis leidyi and its implications for cell type evolution. Science, 342(6164):1242592. 2013. [PubMed]
Solomon BD, Nguyen A-D, Bear KA, Wolfsberg TG. Clinical Genomic Database. Proc Natl Acad Sci U S A, 110(24):9851-5. 2013. [PubMed]
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E. A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies. JAMA Neurol, 70(6):727-735. 2013. [PubMed]
Varshney GK, Lu J, Gildea DE, Huang H, Pei W, Yang Z, Huang SC, Schoenfeld D, Pho NH, Casero D, Hirase T, Mosbrook-Davis D, Zhang S, Jao LE, Zhang B, Woods IG, Zimmerman S, Schier AF, Wolfsberg TG, Pellegrini M, Burgess SM, Lin S. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function. Genome Res, 23(4):727-35. 2013. [PubMed]
Varshney GK, Huang H, Zhang S, Lu J, Gildea DE, Yang Z, Wolfsberg TG, Lin S, Burgess SM. The Zebrafish Insertion Collection (ZInC): a web based, searchable collection of zebrafish mutations generated by DNA insertion. Nucleic Acids Res, 41(Database issue):D861-4. 2013. [PubMed]
Bell DW, Sikdar N, Lee Y-Y, Price JC, Chatterjee R, Park H-D, Fox J, Ishiai M, Rudd ML, Pollock LM, Fogoros SF, Mohamed H, Hanigan CL, NISC, Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF, Borate B, McManus KJ, Stoepel J, Sipahimalani P, Godwin AK, Sgroi DC, Merino MJ, Elliot G, Elkahloun A, Vinson C, Takata M, Mullikin JC, Wolfsberg TG, Hieter P, Lim D-S, and Myung K. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS Genetics, 7(8):e1002245. 2011. [PubMed]
Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, and Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med, 361:1651-61. 2009. [PubMed]
Kim YJ, Kim YS, Larochelle A, Renaud G, Wolfsberg TG, Adler R, Donahue RE, Hematti P, Hong BK, Roayaei J, Akagi K, Riberdy JM, Nienhuis AW, Dunbar CE, and Persons DA. Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells. Blood, 113(22):5434-43. 2009. [PubMed]
Grice EA, Kong HH, Renaud G, Young AC, NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. A diversity profile of the human skin microbiota. Genome Research, 18:1043-1050. 2008. [PubMed]
Crawford GE, Davis S, Scacheri PC, Renaud G, Halawi MJ, Erdos MR, Green R, Meltzer PS, Wolfsberg TG, Collins FS. DNase-chip: A high resolution method to identify DNAase I hypersensitive sites using tiled microarrays. Nature Methods, 3:503-509. 2006. [PubMed]
Crawford GE, Holt IE, Whittle J, Webb BD, Tai D, Davis S, Margulies EH, Chen Y, Bernat JA, Ginsburg D, Zhou D, Luo S, Vasicek TJ, Wolfsberg TG, and Collins FS. Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Research, 16:123-131. 2006. [PubMed]
Hematti P, Hong BK, Ferguson C, Adler R, Hanawa H, Sellers S, Holt IE, Eckfeldt CE, Sharma Y, Schmidt M, von Kalle C, Persons DA, Billings EM, Verfaillie CM, Nienhuis AW, Wolfsberg TG, Dunbar CE, and Calmels B. Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells. PLoS Biology, 2:2183-2190. 2004. [PubMed]
Instructional Videos
Current Topics in Genome Analysis 2014 Series
Genome-Scale Sequence Analysis
Book Chapters and Guides
Wolfsberg T.G., Wetterstrand K.A., Guyer M.S., Collins F.S., and Baxevanis A.D. A User's Guide to the Human Genome II. Nature Genetics: Supplement 35: 1-79. 2003. [Full Text]
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Publications
Rudd ML, Mohamed H, Price JC, O'Hara AJ, Le Gallo M, Urick ME; NISC Comparative Sequencing Program, Cruz P, Zhang S, Hansen NF, Godwin AK, Sgroi DC, Wolfsberg TG, Mullikin JC, Merino MJ, Bell DW. Mutational analysis of the tyrosine kinome in serous and clear cell endometrial cancer uncovers rare somatic mutations in TNK2 and DDR1. BMC Cancer, 14:884. 2014. [PubMed]
Renaud G, LaFave MC, Liang J, Wolfsberg TG, Burgess SM. trieFinder: an efficient program for annotating Digital Gene Expression (DGE) tags. BMC Bioinformatics, 15:329. 2014. [PubMed]
Moreland RT, Nguyen AD, Ryan JF, Schnitzler CE, Koch BJ, Siewert K, Wolfsberg TG, Baxevanis AD. A customized Web portal for the genome of the ctenophore Mnemiopsis leidyi. BMC Genomics, 15(1):316. 2014. [PubMed]
Lafave MC, Varshney GK, Gildea DE, Wolfsberg TG, Baxevanis AD, Burgess SM. MLV integration site selection is driven by strong enhancers and active promoters. Nucleic Acids Res, 42(7):4257-69. 2014. [PubMed]
Ryan JF, Pang K, Schnitzler CE, Nguyen AD, Moreland RT, Simmons DK, Koch BJ, Francis WR, Havlak P; NISC Comparative Sequencing Program, Smith SA, Putnam NH, Haddock SH, Dunn CW, Wolfsberg TG, Mullikin JC, Martindale MQ, Baxevanis AD. The genome of the ctenophore Mnemiopsis leidyi and its implications for cell type evolution. Science, 342(6164):1242592. 2013. [PubMed]
Solomon BD, Nguyen A-D, Bear KA, Wolfsberg TG. Clinical Genomic Database. Proc Natl Acad Sci U S A, 110(24):9851-5. 2013. [PubMed]
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E. A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies. JAMA Neurol, 70(6):727-735. 2013. [PubMed]
Varshney GK, Lu J, Gildea DE, Huang H, Pei W, Yang Z, Huang SC, Schoenfeld D, Pho NH, Casero D, Hirase T, Mosbrook-Davis D, Zhang S, Jao LE, Zhang B, Woods IG, Zimmerman S, Schier AF, Wolfsberg TG, Pellegrini M, Burgess SM, Lin S. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function. Genome Res, 23(4):727-35. 2013. [PubMed]
Varshney GK, Huang H, Zhang S, Lu J, Gildea DE, Yang Z, Wolfsberg TG, Lin S, Burgess SM. The Zebrafish Insertion Collection (ZInC): a web based, searchable collection of zebrafish mutations generated by DNA insertion. Nucleic Acids Res, 41(Database issue):D861-4. 2013. [PubMed]
Bell DW, Sikdar N, Lee Y-Y, Price JC, Chatterjee R, Park H-D, Fox J, Ishiai M, Rudd ML, Pollock LM, Fogoros SF, Mohamed H, Hanigan CL, NISC, Zhang S, Cruz P, Renaud G, Hansen NF, Cherukuri PF, Borate B, McManus KJ, Stoepel J, Sipahimalani P, Godwin AK, Sgroi DC, Merino MJ, Elliot G, Elkahloun A, Vinson C, Takata M, Mullikin JC, Wolfsberg TG, Hieter P, Lim D-S, and Myung K. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5. PLoS Genetics, 7(8):e1002245. 2011. [PubMed]
Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, and Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med, 361:1651-61. 2009. [PubMed]
Kim YJ, Kim YS, Larochelle A, Renaud G, Wolfsberg TG, Adler R, Donahue RE, Hematti P, Hong BK, Roayaei J, Akagi K, Riberdy JM, Nienhuis AW, Dunbar CE, and Persons DA. Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells. Blood, 113(22):5434-43. 2009. [PubMed]
Grice EA, Kong HH, Renaud G, Young AC, NISC Comparative Sequencing Program, Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA. A diversity profile of the human skin microbiota. Genome Research, 18:1043-1050. 2008. [PubMed]
Crawford GE, Davis S, Scacheri PC, Renaud G, Halawi MJ, Erdos MR, Green R, Meltzer PS, Wolfsberg TG, Collins FS. DNase-chip: A high resolution method to identify DNAase I hypersensitive sites using tiled microarrays. Nature Methods, 3:503-509. 2006. [PubMed]
Crawford GE, Holt IE, Whittle J, Webb BD, Tai D, Davis S, Margulies EH, Chen Y, Bernat JA, Ginsburg D, Zhou D, Luo S, Vasicek TJ, Wolfsberg TG, and Collins FS. Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Research, 16:123-131. 2006. [PubMed]
Hematti P, Hong BK, Ferguson C, Adler R, Hanawa H, Sellers S, Holt IE, Eckfeldt CE, Sharma Y, Schmidt M, von Kalle C, Persons DA, Billings EM, Verfaillie CM, Nienhuis AW, Wolfsberg TG, Dunbar CE, and Calmels B. Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells. PLoS Biology, 2:2183-2190. 2004. [PubMed]
Instructional Videos
Current Topics in Genome Analysis 2014 Series
Genome-Scale Sequence AnalysisBook Chapters and Guides
Wolfsberg T.G., Wetterstrand K.A., Guyer M.S., Collins F.S., and Baxevanis A.D. A User's Guide to the Human Genome II. Nature Genetics: Supplement 35: 1-79. 2003. [Full Text]
Last updated: March 24, 2022