Connecting Sequence and Biology in the Laboratory Mouse

Abstract

The Mouse Genome Sequencing Consortium and the RIKEN Genome Exploration Research group have generated large sets of sequence data representing the mouse genome and transcriptome, respectively. These data provide a valuable foundation for genomic research. The challenges for the informatics community are how to integrate these data with the ever-expanding knowledge about the roles of genes and gene products in biological processes, and how to provide useful views to the scientific community. Public resources, such as the National Center for Biotechnology Information (NCBI; http://www.ncbi.nih.gov), and model organism databases, such as the Mouse Genome Informatics database (MGI; http://www.informatics.jax.org), maintain the primary data and provide connections between sequence and biology. In this paper, we describe how the partnership of MGI and NCBI LocusLink contributes to the integration of sequence and biology, especially in the context of the large-scale genome and transcriptome data now available for the laboratory mouse. In particular, we describe the methods and results of integration of 60,770 FANTOM2 mouse cDNAs with gene records in the databases of MGI and LocusLink.Large-scale sequencing and annotation efforts, such as the human and mouse genome sequencing initiatives (Lander et al 2001;Waterston et al. 2002), the RIKEN full-length enriched cDNA sequencing project (Kawai et al. 2001;Okazaki et al. 2002), and the Mammalian Gene Collection (MGC; Strausberg et al. 1999), have made publicly available a wealth of genomic and transcript information to support diverse research efforts related to understanding mammalian biology and disease. Now more than ever, users need easy access to integrated views of, and analysis tools for, high-quality information about mammalian genes and genomes. The challenge is to develop strategies for integrating these data with continually emerging knowledge about the function, variation, and regulation of genes and other genomic features. The collaboration between the Mouse Genome Informatics (MGI) group 8 and the National Center for Biotechnology Information's (NCBI) LocusLink and RefSeq groups (http:// www.ncbi.nih.gov/) exemplifies how coordinated efforts facilitate connectivity between sequence and biology in the mouse. The MGI resource provides highly integrated and curated views of genetic, genomic, and biological data for the laboratory mouse. LocusLink, through the Reference Sequence (RefSeq) project, connects biological information to the sequences of reference chromosomes, RNAs, and proteins. The MGI/LocusLink collaboration has its greatest impact through the mutual determination of the sequences which best define mouse genes. Once gene-to-sequence(s) connections are established, and associations to available information about the genes are made, the foundation is set for additional computation, curation, and Internet connectivity for the scientific community.

The Ensembl Core Software Libraries: Figure 1

“…The Grand Unified Schema (Bahl et al 2003) also matured into a successful project. There are several effective in-house RDBMS projects for storing genome information, such as the Saccharomyces Genome Database (Weng et al 2003) and Mouse Genome Informatics (Baldarelli et al 2003). Although these projects provide excellent Web access to their resources, their schemas and code bases are either unavailable or their use is limited.…”

Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

“…The target set was comprised of 2578 annotated clones, representing a workable size subset for this study. Using the RIKEN clone ID number of each potential human disease related target, we identified the representative transcript from RTPS 6.3 [22] to indicate the FANTOM2 cluster representative transcriptional unit associated with disease (see Tables 2, 3, 4). …”

The spatial organization of the genome in mammalian cells

“…It is ironic that the original idea of chromosome territories was deduced from studies of an early embryo [19] and yet this problem has been hardly studied in a developmental context. The sequencing and annotation of the mouse genome is now being completed at a high resolution [65,66] and an international consortium has been formed with the goal of bridging genomics and nuclear organization in the context of mammalian development [7,67,68]. It will be exciting to see the results of interphase chromosome arrangement studies in mouse embryos, and their degree of concordance with parallel studies in somatic mouse and human cell lines.…”