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EnglishThe recent technological advances underlying the screening of large combinatorial libraries in high- throughput mutational scans, deepen our understanding of adaptive protein evolution and boost its applications in protein design. Nevertheless, the large number of possible genotypes requires suitable computational methods for data analysis, the prediction of mutational effects and the generation of optimized sequences. We describe a computational method that, trained on sequencing samples from multiple rounds of a screening experiment, provides a model of the genotype-fitness relationship. We tested the method on five large-scale mutational scans, yielding accurate predictions of the mutational effects on fitness. The inferred fitness landscape is robust to experimental and sampling noise and exhibits high generalization power in terms of broader sequence space exploration and higher fitness variant predictions. We investigate the role of epistasis and show that the inferred model provides structural information about the 3D contacts in the molecular fold.
Unsupervised inference of protein fitness landscape from deep mutational scan / Fernandez-de-Cossio-Diaz, Jorge; Uguzzoni, Guido; Pagnani, Andrea. - In: MOLECULAR BIOLOGY AND EVOLUTION. - ISSN 0737-4038. - ELETTRONICO. - 38:1(2021), pp. 318-328.
| Titolo: | Unsupervised inference of protein fitness landscape from deep mutational scan |
| Autori: | |
| Data di pubblicazione: | 2021 |
| Rivista: | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1093/molbev/msaa204 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2020.03.18.996595v1.full (1).pdf | 2. Post-print / Author's Accepted Manuscript |  | Visibile a tuttiVisualizza/Apri | |
| msaa204.pdf | Advance Access publication | 2a Post-print versione editoriale / Version of Record | Non Pubblico - Accesso privato/ristretto | Administrator Richiedi una copia |
| msaa204.pdf | 2a Post-print versione editoriale / Version of Record | | Visibile a tuttiVisualizza/Apri |
http://hdl.handle.net/11583/2842668
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