Understanding and predicting protein variant effects through complementarity, disagreement, and consensus

PhD defence by Nicolas Fjord Jonsson

Assessment Committee

Professor Kaare Teilum, Biology, University of Copenhagen (Chairperson)
Associate Professor Elena Papaleo, DTU
Professor Grzegorz Kudla, University of Edinburgh

Supervisors

Professor Kresten Lindorff-Larsen

Department

Department of Biology

Place

Building: Copenhagen Biocenter, Room: 1.2.03, Ole Maaløes Vej 5, 2200 København

Email address to gain access to the thesis: nicolas.jonsson@icloud.com.
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Short description of the thesis

Every protein in the body is built from a blueprint written in DNA, and a single change to that blueprint — a missense variant — can disrupt how a protein folds or functions, a major cause of genetic disease. Genome sequencing now uncovers variants faster than experiments can test them, so computational predictors estimate their effects. But many such predictors exist, and they often disagree. This thesis asks not how to build a better predictor, but how to make better use of the ones we have — comparing them to uncover a variant's mechanism, to target scarce experimental resources, and to build a reliable consensus for protein families that are hard to study experimentally, resolving variants that experiments alone cannot.