Publication date: September 2019
Suggested citation: U.S. DOE. 2019. Breaking the Bottleneck of Genomes: Understanding Gene Function Across Taxa Workshop Report, DOE/SC-0199, U.S. Department of Energy Office of Science. genomicscience.energy.gov/ genefunction/.
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Summary: In the last few decades, high-throughput technologies using various “omics” have enabled unprecedented views of biological systems at the molecular level. In parallel, the integration of omic datasets using computational modeling has provided new understanding of biological processes in organisms relevant to the U.S. Department of Energy’s (DOE) missions in energy and the environment. Collectively, these developments have spearheaded the advancement of systems biology, which can be viewed as a holistic approach for deciphering the complexity of biological systems. However, as high-throughput omic technologies and integrative systems biology efforts have improved our understanding of some biological systems, analyzing and finding meaningful answers within these massive datasets remain extremely challenging, in large part due to the lack of fundamental knowledge of gene function. Indeed, all sequenced genomes, both microbes and plants, contain large numbers of genes of “unknown function” that significantly limit scientists’ ability to model, predict, and engineer organisms with enhanced functions relevant to DOE. Current methodologies can be employed to decipher gene function, but they are typically slow, laborious, inefficient, and not scalable.
This “bottleneck” in genome understanding could be broken with new, innovative, and transformative experimental tools, datasets, and computation that can define gene function on a massive and high-throughput scale compatible with the pace of DNA sequencing. In light of this grand challenge, DOE’s Office of Biological and Environmental Research (BER) convened the Breaking the Bottleneck of Genomes: Understanding Gene Function Across Taxa workshop on November 1–2, 2018. This workshop brought together leaders in microbiology, plant sciences, technology, and computation, who collectively identified the experimental and data analysis gaps preventing large-scale gene function determination as well as opportunities for overcoming these gaps.
The workshop was organized around breakout sessions in which participants discussed research challenges associated with gene function discovery and accurate annotation across taxa. The discussions included the breadth of diverse, high-throughput technologies needed for characterizing genes of unknown function and how the diverse data from these technologies could be integrated with new and existing computational platforms to accurately propagate these annotations to newly sequenced genomes. While many of these technological and computational challenges are universal across taxa, the workshop organizers recognized that organism-specific biology and experimental limitations would prevent the development of unified solutions. Thus, separate breakout sessions were held for plants and microorganisms, which represent the most significant BER investment in genomic sciences. This report presents the challenges, knowledge gaps, and opportunities for accelerated gene function discovery and accurate gene annotation in four areas: technology, computation, microorganisms, and plants. Each of these areas is framed by the charge questions posed to all the participants and discussed at the workshop.