The Jackson Laboratory

Overview

Our research program focuses on two major areas: bioinformatics and developmental genomics. In the area of bioinformatics we focus on building information systems that can facilitate the use of the laboratory mouse as a model system for understanding normative biology and disease processes in humans. We are members of the Mouse Genome Informatics (MGI) consortium and work collaboratively with other investigators at The Jackson Laboratory to build and maintain databases that contain the most comprehensive collection of integrated functional genetic and genomic data for the laboratory mouse available in the public domain. In addition to the MGI information system, we also maintain the Mouse Phenome Database, which contains baseline phenotype measurement for hundreds of traits across scores of inbred lines of mice. Recent projects include the release of a comprehensive gene catalog for the reference mouse genome assembly and the release of MouseCyc, a database of curated biochemical pathways in the laboratory mouse.

In the area of developmental genomics, we are working in collaboration with Dr. Isaac Kohane (Children's Hospital Boston) to use an understanding of the molecular genetics of normal lung development in mouse as a framework for identifying key genes and pathways in lung diseases such as cancer and pulmonary fibrosis. Recent projects include generating an integrated data set of mRNA and microRNA profiles over several key developmental time points in murine lung development.

Scientific report

Bridging the digital biology divide

The Mouse Genome Sequences and Maps Group: Integrating sequence and biology in the Mouse Genome Informatics (MGI) database

The mission of the Mouse Genome Informatics (MGI) database consortium is to facilitate the use of the mouse as a model system for understanding human biological processes and disease. As part of the MGI consortium, the Mouse Genome Sequences and Maps group has as its mission to connect mouse sequence data with the wealth of biological knowledge about mouse genes available in the MGI database. We accomplish our mission by:

• curating associations between sequences and genes;
• building a complete and non-redundant catalog of mouse genes;
• associating genes in MGI with relevant data in external databases;
• supporting sequence-based queries of MGI using our customized MouseBLAST server; and
• supporting the generation of customized data sets of sequences using biologically meaningful criteria (e.g., "Return all protein sequences for genes on Chromosome 2 that have been annotated as transcription factors").

Two highlights of the Mouse Genome Sequences and Maps group in the past year include the release of a unified gene catalog for the reference mouse genome assembly and the incorporation of microRNA genes into the MGI database. The goal of the unified gene catalog project was to generate a single list of all known and predicted mouse genes. This project was facilitated by an efficient computational algorithm developed by fellow MGI consortium member, Dr. Joel Richardson. Dr. Richardson's algorithm allowed us to compare tens of thousands of gene predictions for the mouse genome generated independently by three different external bioinformatics groups to determine which predictions represented the same gene and which predictions were unique to a particular annotation pipeline. The results of the unified gene catalog project are available from the MGI database. The increased recognition of the importance of non-coding genes such as microRNAs for transcription regulation and disease prompted us to incorporate what is known about more than 370 known mouse microRNAs into MGI. This project was done in collaboration with the microRNA database group (miRBase) at the Sanger Institute in the United Kingdom.

See scientific reports in this volume by Drs. Janan Eppig, Martin Ringwald, and Judith Blake for information about additional projects related to the MGI database consortium (http://www.informatics.jax.org).

The Mouse Tumor Biology (MTB) database

The MTB database is the most comprehensive publicly accessible database on cancer characteristics in inbred and genetically-modified strains of mice. The data in MTB include strain characteristics for hyperplasias and neoplasias, histopathology reports and images, and tumor genetics. Data are obtained both from the primary literature and by direct submissions from cancer researchers. MTB is accessed via the Mouse Genome Informatics web site (http://www.informatics.jax.org). During the past year, the infrastructure for MTB was completely redesigned and upgraded. New query interfaces were implemented and a new pathology data submission tool was released.

Data management for large-scale animal husbandry and phenotyping

The JaxTrack laboratory information system supports workflow, data management, and data analysis associated with mutagenesis, animal husbandry, sample tracking, and phenotype analysis for the Heart, Lung, Blood and Sleep Disorders Center, the Nathan Shock Center of Excellence in Basic Biology of Aging, and the Center for Genome Dynamics. JaxTrack supports workflow management, data review, database queries, and project status reports. Much of the phenotyping data managed in the JaxTrack system is made available (after expert data review) to the scientific community via the Mouse Phenome Database (MPD). The JaxTrack project was recently integrated into the Computational Sciences Service to support optimal coordination with related software development projects at The Jackson Laboratory.

Mouse Phenome Database (MPD)

The Mouse Phenome Database (MPD) is a comprehensive resource for phenotypic information on commonly used inbred mouse strains. Through MPD, researchers can access and download measurement data for individual animals and details about the phenotyping protocols for each data set. The Web-based interfaces for MPD support basic statistical analyses and comparisons of data across or within strains and studies. The detailed phenotype information in MPD combined with increasingly dense maps of sequence variation for inbred lines of mice make this resource indispensable for in silico mapping experiments and for identifying appropriate mouse strains for drug testing, toxicology studies, complex trait analysis, and human disease models. The MPD database project is a collaborative effort involving academic and industry research labs from all over the world.

See the scientific report in this volume by Dr. Molly Bogue for more information and recent updates about the Mouse Phenome Database project.

MouseCyc: A biochemical pathways database for the laboratory mouse

The availability of the complete genome sequence for the C57BL/6J strain of laboratory mouse provides a powerful platform for predicting genes and other genome features. However, building a catalog of genome annotations is just the beginning for biology in a "post-genome" era. To gain new insights into fundamental biological processes using complete genome sequences and related genome-scale data will require understanding how genome features interact in pathways and networks in the cell and how perturbations of these interactions contribute to normal biological and disease processes.

The MouseCyc database is a new resource for exploring the biology of the laboratory mouse in the context of biochemical pathways. MouseCyc represents a significant step forward in providing researchers with access to mouse genomic data in the context of physiological and cellular processes. The initial focus for the development of MouseCyc will be on metabolism that includes such cell level processes as biosynthesis, degradation, energy production, and detoxification. MouseCyc is unique relative to other pathway databases because the resource incorporates the rich biological knowledge about mouse genes and phenotypes that is available from the Mouse Genome Informatics (MGI) database.

Lab staff

Principal Investigator Carol J. Bult, Ph.D., Associate Professor Co-Principal Investigators Janan T. Eppig, Ph.D., Professor Judith A. Blake, Ph.D., Associate Professor Joel E. Richardson, Ph.D., Senior Research Scientist James A. Kadin, Ph.D., Senior Research Scientist Research Scientist Molly A. Bogue, Ph.D. Senior Scientific Curators Dale Bagley, Ph.D. Dirck W. Bradt, M.S. Debra M. Krupke, M.S. Yunzia "Sophia" Zhu, Ph.D.

Scientific Curators Robert Sinclair, Ph.D. TBK Reddy, Ph.D. Kenneth S. Frazer, M.S. Terry Maddatu, Ph.D. Scientific Curator Assistant Deborah J. Reed Bioinformatics Analyst Mary Dolan, M.S., Ph.D. Software Engineers Nazira Bektassova, Ph.D. Abigail Miller, B.S. Stephen C. Grubb, M.S. Research Administrative Assistant Daron McGowan

Publication listings

Publications 2002-Present

Blake JA, Bult CJ, Eppig JT, Kadin JA, Richardson JE; The Mouse Genome Database Group. 2009. The Mouse Genome Database genotypes::phenotypes. Nucleic Acids Res.37 37(Database):D712-9.

Grubb SC, Maddatu TP, Bult CJ, Bogue MA. 2009. Mouse phenome database. Nucleic Acids Res. 37(Database):D720-30.

Bult CJ, Eppig JT, Kadin JA, Richardson JE, Blake JA; Mouse Genome Database Group. 2008. The Mouse Genome Database (MGD): mouse biology and model systems. Nucleic Acids Res. 36(Database):D724-8.

Guan Y, Myers CL, Lu R, Lemischka IR, Bult CJ, Troyanskaya OG. 2008. A genomewide functional network for the laboratory mouse. PLoS Comput Biol. 4(9):e1000165.

Krupke DM, Begley DA, Sundberg JP, Bult CJ, Eppig JT. 2008. The Mouse Tumor Biology database. Nat Rev Cancer 8(6):459-65.

Naxerova K, Bult CJ, Peaston A, Fancher K, Knowles BB, Kasif S, Kohane IS. 2008. Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Genome Biology 9(R108):R108.

Eppig JT, Blake JA, Bult CJ, Richardson JE, Kadin JA, Ringwald M and the MGI Staff.  2007.  Mouse Genome Informatics(MGI) resources for pathology and toxicology.   Toxicol Pathol 35:456-7.

Begley DA, Krupke DM, Vincent MJ, Sundberg JP, Bult CJ, Eppig JT.   2007.  Mouse Tumor Biology Database(MTB):  status, update, and future directions. Nucleic Acids Res. 35:D638-42.

Bogue MA, Grubb SC,  Maddatu TP, Bult CJ.  2007.  Mouse Phenome Databse (MPD). Nucleic Acids Res 35:643-9.

Bouma GJ, Affourtit JP, Bult CJ, Eicher EM.  2007.  Transcriptional profile of  mouse pre-granulosa and Sertoli cells isolated from early-differentiated fetal gonads. Gene Expr Patterns  7:113-23.

Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE, Mouse Genome Database Group.   2007.  The mouse genome database (MGD): new features facilitating a model system. Nucleic Acids Res. 35: D630-7.

Kim S, Huang LW, Snow KJ, Ablamunits V, Hasham MG, Young TH, Paulk AC, Richardson JE, Affourtit JP, Shalom-Barak T, Bult CJ, Barak Y. 2007. A mouse model of conditional lipodystrophy. Proc Natl Acad Sci U S A 104(42):16627-32.

Peters LL, Robledo RF, bult CJ, Churchill GA, Paigen BA, Svenson KL.  2007. The mouse as a model for human biology: a resource guide for complex trait analysis. Nat Rev Genet 8:58-59.

Dolan ME, Holden C, Beard MK, and Bult CJ. 2006.  Genomes as geography: using GIS technology to build interactive genome feature maps. BMC Bioinformatics7:416.

Shopland LS, Lynch CR, Peterson KA, Thornton K, Kepper N, von Hase J, Vincent S, Molloy KR, Kreth G, Cremer C, Bult CJ, and O'Brien TP. 2006. Gene distrubution pattern in gene-poor primary sequence defines higher-order chromatin structures. J Cell Biol 174(1):27-38. 

Furuno M, Pang KC, Ninomiya N, Fukuda S,  Firth MC, Bult CJ, Mattick JS and Suzuki H. 2006.  Clustering of internally-primed transcripts reveals novel long non-coding RNAs. PLOS Genetics, 2(4):e37.

Blake JA and Bult CJ. 2006.  Beyond the data deluge. Biomedical Informatics 39(3):314-320.

Bult CJ. 2006. From information to understanding: The role of model organism databases in comparative and functional genomics. Animal Genetics, 37(S1):28-48.

Gene Ontology Consortium. 2006.  The Gene Ontology(GO) Project in 2006. Nucl.Acids Res. 34:D322-D326.

The FANTOM Consortium and The RIKEN Genome Exploration Research Group. 2005.
the Transcriptional Landscae of the Mammalian Genome. Science 309.1559-1563. (One of the core authors).

Krupke DM, Naf D, Vincent MJ, Allio T, Mikaelian I, Sundberg JP, Bult CJ, Eppig JT. 2005. The Mouse Tumor Biology Database: intergrated access to mouse cancer biology data. Exp Lung Res 31(2):259-270.

Richardson JE, Kadin JA, Blake JA, Bult CJ, Eppig JT, Ringwald M and the Mouse Genome Informatics Group. 2004. From sipping on a straw to drinking from a fire hose; data integration in a public genome database. Proceedings of the 20th IEEE International Conference on Data Engineering, Boston MA, March 2004, pp795-798.

Bult CJ, Kibbe WA, Snoddy J, Vitaterna M, Swanson D, Pretel S, Li Y, Hohman MM, Rinchik E, Takahashi JS, Frankel WN, Goldowitz D. 2004. A genome end - game:  understanding gene function n the nervous system. Nat Neurosci 7(5):484-5. 

Mikaelian I, Nanney LB, Parman KS, Kusewitt DF, Ward JM, Naf D, Krupke DM, Eppig JT, Bult CJ, Seymour R, Ickiki T, Sundberg JP. 2004. Antibodies that label paraffin-embedded mouse tissues: a collaborative endeavor. Toxicol Pathol 32(2): 181-91.

Gene Ontology Consortium. 2004. The Gene Ontology(GO) database and informatics resource. Nucleic Acids Res. 1(32).

Goldowitz D, Frankel WN, Takahashi JS, Holtz-Vitaterna M, Bult C, Kibbe WA, Snoddy J, Li Y, Pretel S, Yates J, Swanson DJ. 2004. Large -scale mutagenesis of the mouse to understand the genetic base of nervous system structure and function. Molec Brain Res 132:105-115.

Evsikov A, Vries WN, Peaston AE, Radford EE, Fancher KS, Chen FH, Blake JA, Bult CJ, Latham KE, Soltor D, Knowles BB. 2004. Systems biology of the 2-cell mouse embryo. Cytogenet Genome Res. 105:240-250.

Bult CJ, Blake JA, Richardson JE, Kadin JA, Eppig JT, and the members of The Mouse Genome Database Group. 2004.  The Mouse Genome Database(MGD): Integrating biology with the genome. Nucleic Acids REs. 1(32).

O'Brien TP, Bult CJ, Cremer C, Grunze M, Knowles BB, Langowski J, McNally J, Pederson T, Politz J, Pombo A, Schmahl G, Spatz JP, vanDriel R. 2003.  Genome function and nuclear archiecture: gene expression as nanoscience. Genome Res.13:1029-1041.

Blake JA, Richardson JE, Bult CJ, Kadin JA, Eppig JT, and Members of the Mouse Genome Database Group. 2003. MGD: The Mouse Genome Database. Nucleic Acids
Res 31:193-195.

Bult CJ. 2003. Mice and More. Genome Biol. 4(10):340.

Kasukawa T, Furuno M, Nikaido L, Bono H, Hume BA, Bult CJ, Hill DP, Baldardelli R, Gough J, Kanapin A, Matsuda H, Schriml LM, Hayashizaki Y, Olazaki Y, Quackenbush J. 2003. Development and evaluation of an automated annotation pipline and cDNA annotation system. Genome Res. 13(6B):1542-51.

Zhu Y, King BL, Parvizi B, Brunks B, Stoeckert C, Quackenbush J, Richardson J, Bult CJ. 2003. Integrating computationally assembled mouse transcript sequences with the Mouse Genome Informatics (MGI) database. Genome Biology 4:R16.

Bult CJ. 2002. Data integration standards in model organisms: from genotype to phenotype in the laboratory mouse. Targets/Drug Discovery Today 1:163-168.

Dolan M, Holden C, Beard MK, Bult CJ. 2002. GenoSIS: Genome Data Interpretation Using GIS. 2002. Proceedings of the Environmental Systems Research Institute, http://gis.esri.com/library/userconf/proc02/pap0719/p0719.htm.

Mouse Genome Sequencing Consortium and Mouse Genome Analysis Group. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520-562.

N?f D, Krupke DM, Sundberg JP, Eppig JT, Bult CJ. 2002. The mouse tumor biology database:  a public resource for cancer genetics and pathology of the mouse.  Cancer Res 62:1235-1240.

Peterson KA, King BL, Hagge-Greenberg A, Roix JJ, Bult CJ, and O'Brien TP.  2002. Functional and comparative genomic analysis of the piebald deletion region of mouse chromosome 14. Genomics 80:172-184.

The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I & II Team. 2002. Analysis of the mouse transcriptome based upon functional annotation of 60,770 full length cDNAs. Nature 420:563-573.

Books, Book Chapters, and Reviews

Sundberg JP and Bult CJ. 2006.  Professional use of mutant laboratory mice in research. In:  Handbook on Genetically Engineered Mice. JP Sundberg and T Ichiki(eds.). CRC Press Taylor and Francis Group. pp. 185-209.

Bult CJ, Krupke DM, Vincent MJ, Allio T, Sundberg JP, Mikaelian I, and Eppig JT. 2006.  The Mouse Tumor Biology Database: An online resource for mouse models of human cancer. In: Cancer Bioinformatics: From therap  Design to Treatment(S. Nagl, ed.) John Wiley and Sons. pp 143-153.

Woychik R and Bult CJ. 2005.  Functional analysis of genes. In: Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. LB Jorde, PFR Little, MJ Dunn and S. Subramaniam(eds.)John Wiley and Sons LTD. 1135-41.

Blake J, Eppig JT, Bult CJ. 2006. Mouse and Rat Genome Informatics.  In:  Bioinformatics for Geneticists, Barnes MR, Gray IC, [eds], John Wiley and Sons, London

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