ACIDES: On-line Monitoring of Forward Genetic Screens for Protein Engineering

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Dec 26

PMID 38148337

Authors

Takahiro Nemoto

Tommaso Ocari

Arthur Planul

Muge Tekinsoy

Emilia A Zin

Deniz Dalkara

Ulisse Ferrari

Affiliations

Soon will be listed here.

Abstract

Forward genetic screens of mutated variants are a versatile strategy for protein engineering and investigation, which has been successfully applied to various studies like directed evolution (DE) and deep mutational scanning (DMS). While next-generation sequencing can track millions of variants during the screening rounds, the vast and noisy nature of the sequencing data impedes the estimation of the performance of individual variants. Here, we propose ACIDES that combines statistical inference and in-silico simulations to improve performance estimation in the library selection process by attributing accurate statistical scores to individual variants. We tested ACIDES first on a random-peptide-insertion experiment and then on multiple public datasets from DE and DMS studies. ACIDES allows experimentalists to reliably estimate variant performance on the fly and can aid protein engineering and research pipelines in a range of applications, including gene therapy.

Citing Articles

ACIDES: on-line monitoring of forward genetic screens for protein engineering.

Nemoto T, Ocari T, Planul A, Tekinsoy M, Zin E, Dalkara D Nat Commun. 2023; 14(1):8504.

PMID: 38148337 PMC: 10751290. DOI: 10.1038/s41467-023-43967-9.

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