Abstract
The genotype-phenotype relationship defines evolution in the long run and human health day to day. Because it is rooted in randomness and cryptic selection forces exerted over individuals but mirrored in DNA, this relationship seems intractably complex. Surprisingly, when we frame it formally in fitness landscapes, we find that genes and their mutations obey quantitative rules from statistical physics with characteristic differences in health and disease. In practice, these rules consistently point to genes relevant to population risk of complex diseases, as examples in cancer, autism, Alzheimer’s and diabetes will show.
Some publications
- Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli. Marciano DC, Wang C, Hsu TK, Bourquard T, Atri B, Nehring RB, Abel NS, Bowling EA, Chen TJ, Lurie PD, Katsonis P, Rosenberg SM, Herman C, Lichtarge O. Nat Commun. 2022 Jun 9;13(1):3189. doi: 10.1038/s41467-022-30889-1.
PMID: 35680894
- Genome interpretation using in silico predictors of variant impact. Katsonis P, Wilhelm K, Williams A, Lichtarge O. Hum Genet. 2022 Apr 30:1-29. doi: 10.1007/s00439-022-02457-6. Online ahead of print. PMID: 35488922
- EPIMUTESTR: a nearest neighbor machine learning approach to predict cancer driver genes from the evolutionary action of coding variants. Parvandeh S, Donehower LA, Panagiotis K, Hsu TK, Asmussen JK, Lee K, Lichtarge O. Nucleic Acids Res. 2022 Jul 8;50(12):e70. doi: 10.1093/nar/gkac215. PMID: 35412634
- A general calculus of fitness landscapes finds genes under selection in cancers. Hsu TK, Asmussen J, Koire A, Choi BK, Gadhikar MA, Huh E, Lin CH, Konecki DM, Kim YW, Pickering CR, Kimmel M, Donehower LA, Frederick MJ, Myers JN, Katsonis P, Lichtarge O. Genome Res. 2022 May;32(5):916-929. doi: 10.1101/gr.275811.121. Epub 2022 Mar 17. PMID: 35301263
- Recurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors. Huh E, Gallion J, Agosto MA, Wright SJ, Wensel TG, Lichtarge O. Proc Natl Acad Sci U S A. 2021 Dec 21;118(51):e2113373118. doi: 10.1073/pnas.2113373118. PMID: 34916293
- A method to delineate de novo missense variants across pathways prioritizes genes linked to autism. Koire A, Katsonis P, Kim YW, Buchovecky C, Wilson SJ, Lichtarge O. Sci Transl Med. 2021 May 19;13(594):eabc1739. doi: 10.1126/scitranslmed.abc1739.PMID: 34011629
- Identification of evolutionarily stable sites across the SARS-CoV-2 proteome. Wang C, Konecki DM, Marciano DC, Govindarajan H, Williams AM, Wastuwidyaningtyas B, Bourquard T, Katsonis P, Lichtarge O. Res Sq. 2020 Oct 20:rs.3.rs-95030. doi: 10.21203/rs.3.rs-95030/v1. Preprint. PMID: 33106800
- An Evolutionary Trace method defines functionally important bases and sites common to RNA families. Novikov IB, Wilkins AD, Lichtarge O. PLoS Comput Biol. 2020 Mar 24;16(3):e1007583. doi: 10.1371/journal.pcbi.1007583. eCollection 2020 Mar. PMID: 32208421
Invited by Ralf Jockers.
