Rapid advances in genome sequencing techniques and throughput are providing scientists with increasingly detailed views of individual genomes, furthering our understanding of genetic variation in a wide array of organisms, of human population history and of the biology of Mendelian disorders and complex traits. Experiments that were until recently restricted to very large genome centers, such as the resequencing of human genomes, can now be carried out by a wide range of investigators. While these technological advances will enable many new discoveries in human and model organism genetics, they also pose formidable computational challenges. RFA-HG-10-018, entitled """"""""Informatics Tools for High-Throughput Sequence Data Analysis"""""""", is intended to fund further development of existing software to ensure that any biological or biomedical research laboratory can benefit from advances in sequencing technologies. We have developed specialized, state-of-the-art tools for the processing and analysis of next generation sequence data. Our tools encompass many key steps in sequence data analysis, ranging from quality control, to read mapping, to the identification, genotyping and annotation of many classes of sequence variation, to downstream association analyses that seek to connect identified variants with organismal phenotypes. These tools have been used to support analysis of several large, challenging datasets including not only data from the 1000 Genomes Project but also >1000 whole genomes and >2500 exomes sequenced in medical sequencing projects. Here, we propose to develop these tools into easy-to-use, portable, well-documented packages and complete pipelines that facilitate biomedical research in a wide variety of settings. A key component of the proposal is the deployment of these tools in the Galaxy cloud, where they will be accessible to investigators without direct access to a local high-throughput computing and data storage facility.
We are developing computer software to discover and interpret genetic differences between individual human genomes from DNA sequencing data. We are starting with existing computer programs and turning them into stable software packages that can be readily used by any biological laboratory. These methods will enhance the study of human genetic variability and the understanding of heritable human diseases.
| Chiang, Charleston W K; Marcus, Joseph H; Sidore, Carlo et al. (2018) Genomic history of the Sardinian population. Nat Genet 50:1426-1434 |
| Than, Hein; Qiao, Yi; Huang, Xiaomeng et al. (2018) Ongoing clonal evolution in chronic myelomonocytic leukemia on hypomethylating agents: a computational perspective. Leukemia 32:2049-2054 |
| Ostrander, Betsy E P; Butterfield, Russell J; Pedersen, Brent S et al. (2018) Whole-genome analysis for effective clinical diagnosis and gene discovery in early infantile epileptic encephalopathy. NPJ Genom Med 3:22 |
| Steri, Maristella; Orrù, Valeria; Idda, M Laura et al. (2017) Overexpression of the Cytokine BAFF and Autoimmunity Risk. N Engl J Med 376:1615-1626 |
| Ward, Alistair; Karren, Mary A; Di Sera, Tonya et al. (2017) Rapid clinical diagnostic variant investigation of genomic patient sequencing data with iobio web tools. J Clin Transl Sci 1:381-386 |
| van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P et al. (2017) Discovery of novel heart rate-associated loci using the Exome Chip. Hum Mol Genet 26:2346-2363 |
| Khorashad, J S; Tantravahi, S K; Yan, D et al. (2016) Rapid conversion of chronic myeloid leukemia to chronic myelomonocytic leukemia in a patient on imatinib therapy. Leukemia 30:2275-2279 |
| 1000 Genomes Project Consortium; Auton, Adam; Brooks, Lisa D et al. (2015) A global reference for human genetic variation. Nature 526:68-74 |
| Ding, Jun; Sidore, Carlo; Butler, Thomas J et al. (2015) Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools. PLoS Genet 11:e1005306 |
| Fuchsberger, Christian; Abecasis, Gonçalo R; Hinds, David A (2015) minimac2: faster genotype imputation. Bioinformatics 31:782-4 |
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