Whole genome sequencing projects of human and other vertebrates have greatly advanced comparative genomics, which led to novel biological discoveries. Our long-term research goal is to use comparative genomics to elucidate the trajectory of vertebrate genome evolution and the origin of complex traits of different species. Such insights will in turn help us better understand the biology of the human genome. Advances in next-generation sequencing (NGS) technologies have provided us with unprecedented opportunities to tackle this problem. However, the large number of genomes being sequenced and the limitations of genome quality produced by NGS have underlined urgent needs for new computational methods to address several pressing challenges for the new generation of comparative genomic analysis. The objective in this particular application is to develop new computational methods to improve the accuracy of whole- genome comparisons for vertebrate genomes. We have two specific aims: (1) To develop a comparative assembly algorithm to improve vertebrate genomes assembled from NGS data; (2) To develop a probabilistic framework to improve the quality of multiple sequence alignments for vertebrate genomes. Our research plan is innovative because it provides novel algorithms and software tools to systematically improve the foundations for genome comparisons. The research is significant because the methods to be developed will allow researchers to more effectively utilize the new genome sequencing data. The proposed research will have sustained impact even with the increasing number of genomes and the advancement of sequencing technology. By improving the general methodology for next-generation comparative genomics, our work will have a high impact on large-scale genome projects such as G10K and ENCODE. As a result, this innovative project in computational biology will enable advancement in biomedical research.

Public Health Relevance

The proposed research in computational biology is expected to improve comparative genomic analysis to help better understand human biology and disease mechanisms. Thus, this project is relevant to NIH's mission that seeks to obtain fundamental knowledge that will help to enhance health.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
7R01HG007352-03
Application #
9196052
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Wellington, Christopher
Project Start
2014-09-01
Project End
2017-12-31
Budget Start
2016-01-01
Budget End
2016-12-31
Support Year
3
Fiscal Year
2015
Total Cost
$313,654
Indirect Cost
$94,279
Name
Carnegie-Mellon University
Department
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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