Max Alekseyev, Ph.D. - US grants

The proposed project addresses the problem of reconstruction of ancestral genomes and evolutionary history of genomes that may deviate in gene content, resulting from genome rearrangements as well as gene duplications and deletions evolutionary events. It will close the gap between steadily growing number of sequenced genomes and incapability of existing phylogenetic reconstruction tools to process diverse varieties of genomes.

The new PRUGC software will employ the framework of multiple breakpoint graphs that will be extended to address new algorithmic challenges arising from genomes having unequal gene contents. As some of these challenges may be hard and have no computationally feasible solutions, instead of focusing on a fixed evolutionary model and attempting to fit biological problems into it, the PI will let the model be flexible and problem-driven. In the course of PRUGC development, the PI plans to address the following particularly important biological problems (listed in the order of growing complexity): the primate-rodent-carnivore split controversy in mammalian evolution (featuring relatively small number of duplications); phylogenetic analysis of a diverse variety of yeast genomes including genomes that undergone whole genome duplications; and evolutionary problems in plant evolution rich in segmental duplications. Solutions to these problems will help to better understand the mechanisms behind chromosome evolution across variety of genomes. The reconstructed ancestral genomes will provide insights to functional significance of particular gene orders, help to rigorously estimate the rate of genome rearrangements and gene duplications/deletions in different organisms, and allow testing hypotheses about their mechanisms and influence on shaping genomic architectures. It is important to emphasize that the PRUGC software will have a wide range of applications, not limited to the aforementioned problems. The PRUGC software will be helpful in various phylogenomic studies within projects like "Tree of Life", "Genome 10K", and "i5k". It will be released as both a standalone open-source tool and an online web-server application readily accessible for use by biologists.

The project will support research activities in the PI's research lab. In particular, it will help to prepare a new generation of researchers in bioinformatics by providing the opportunities to have hands-on experiences in both computer science and biology. One undergraduate student and two Ph.D. students will be recruited with the support of this project, and the PI will mentor these students and prepare them for building their careers in academia or industry. The PI will make every effort to help the students gain first-hand experience of biology, including short-term visits to our local, national, and international collaborators. Such experience will also help the students to develop and enhance their ability to communicate with researchers in other areas, an important skill in interdisciplinary research.

The project will also offer an excellent opportunity for computer science students to learn about experimental and theoretical research in the interdisciplinary area of bioinformatics. Detailed explanation of the whole process of multiple genomes comparison will perfectly fit into a timeframe of a bioinformatics course. The PI plans to lecture this material within the bioinformatics course CSCE 555 offered for undergraduate and graduate students at the University of South Carolina. As a member of the Bioinformatics Education Alliance developing "Bioinformatics for Biologists" (B4B) textbook, the PI coordinated with the editors preparation of a new chapter module and web-based educational materials for the next edition of B4B that will expand the current chapter on genome rearrangements and illustrate their applications with a number of biological problems within the PRUGC project.

Research in Computational Molecular Biology (RECOMB 2019) is an international scientific conference bridging the computational, mathematical, and biological sciences. The RECOMB conference series was founded in 1997 to provide a scientific forum for theoretical advances in computational biology and their applications in molecular biology and medicine. RECOMB 2019 will be the 23rd Annual Meeting, held in Washington, DC. RECOMB features keynote talks by preeminent scientists, together with presentations of refereed research papers in computational biology, special sessions and poster sessions. This project requests travel support for student conference participants from any US university, with priority going to graduate students who will be presenting paper or posters. Overall, students will be educated on cutting-edge developments that will further drive the research methods and results of the field of computational biology. Students and scientists are able to return to their labs to apply what they have learned as they advance their own research efforts or begin investigating new areas they were exposed to as a result of attending RECOMB. NSF investment in this project will help further students' careers and our nation's competitiveness in an expanding, global industry, and will benefit the public through new discoveries made by highly trained scientists.

The meeting and proposed travel fellowships will have particular value for educational purposes, creating a unique training opportunity for 10 U.S.-based students of computational biology. Awarded travel fellowships will cover registration, hotel, and travel costs for a selected group of student presenters. Preference will be given to students with proceedings papers that are accepted for oral presentation at the conference and secondarily to those making poster presentations of accepted abstracts. Women, minorities and persons with disabilities will be especially encouraged to apply with the goal of achieving diversity at the meeting and directly benefiting diverse groups. As much as possible, participant support cost requested in this grant will be used specifically to fund the travel expenses of students from these three underrepresented groups in order to increase their access to training opportunities. By attending the RECOMB meeting, students will gain the latest skills in computational biology, the field that has the potential to unlock the secrets for understanding life. The field comprises a vibrant, growing industry, with skilled computational scientists in high demand at pharmaceutical, agricultural, environmental, consumer products, biotech, software, hardware, and service companies. Students' participation is vital for the growth and continuation of the field.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.