Improving protein optimization with smoothed fitness landscapes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68407700%3A21730%2F24%3A00380726" target="_blank" >RIV/68407700:21730/24:00380726 - isvavai.cz</a>

Výsledek na webu

<a href="https://openreview.net/forum?id=rxlF2Zv8x0" target="_blank" >https://openreview.net/forum?id=rxlF2Zv8x0</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Improving protein optimization with smoothed fitness landscapes

Popis výsledku v původním jazyce

The ability to engineer novel proteins with higher fitness for a desired property would be revolutionary for biotechnology and medicine. Modeling the combinatorially large space of sequences is infeasible; prior methods often constrain optimization to a small mutational radius, but this drastically limits the design space. Instead of heuristics, we propose smoothing the fitness landscape to facilitate protein optimization. First, we formulate protein fitness as a graph signal then use Tikunov regularization to smooth the fitness landscape. We find optimizing in this smoothed landscape leads to improved performance across multiple methods in the GFP and AAV benchmarks. Second, we achieve state-of-the-art results utilizing discrete energy-based models and MCMC in the smoothed landscape. Our method, called Gibbs sampling with Graph-based Smoothing (GGS), demonstrates a unique ability to achieve 2.5 fold fitness improvement (with in-silico evaluation) over its training set. GGS demonstrates potential to optimize proteins in the limited data regime. Code: https://github.com/kirjner/GGS

Název v anglickém jazyce

Improving protein optimization with smoothed fitness landscapes

Popis výsledku anglicky

The ability to engineer novel proteins with higher fitness for a desired property would be revolutionary for biotechnology and medicine. Modeling the combinatorially large space of sequences is infeasible; prior methods often constrain optimization to a small mutational radius, but this drastically limits the design space. Instead of heuristics, we propose smoothing the fitness landscape to facilitate protein optimization. First, we formulate protein fitness as a graph signal then use Tikunov regularization to smooth the fitness landscape. We find optimizing in this smoothed landscape leads to improved performance across multiple methods in the GFP and AAV benchmarks. Second, we achieve state-of-the-art results utilizing discrete energy-based models and MCMC in the smoothed landscape. Our method, called Gibbs sampling with Graph-based Smoothing (GGS), demonstrates a unique ability to achieve 2.5 fold fitness improvement (with in-silico evaluation) over its training set. GGS demonstrates potential to optimize proteins in the limited data regime. Code: https://github.com/kirjner/GGS

Druh

D - Stať ve sborníku

CEP obor

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OECD FORD obor

10201 - Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8)

Projekt

<a href="/cs/project/EF15_003%2F0000468" target="_blank" >EF15_003/0000468: Inteligentní strojové vnímání</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

Proceeding The Twelfth International Conference on Learning Representations (ICLR 2024)

ISBN

9781713898658

ISSN

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e-ISSN

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Počet stran výsledku

19

Strana od-do

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Název nakladatele

International Conference on Learning Representations

Místo vydání

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Místo konání akce

Vídeň

Datum konání akce

7. 5. 2024

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

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