Determining in vivo protein structures and understanding genetic interactions using deep mutagenesis

Project Information

MUTANOMICS

Grant agreement ID: 883742

DOI

10.3030/883742

Project closed

EC signature date 23 July 2020

Start date 1 January 2021

End date 31 December 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 333 279,00

EU contribution

€ 2 333 279,00

Coordinated by

FUNDACIO CENTRE DE REGULACIO GENOMICA
Spain

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Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Publications

Peer reviewed articles (21)

DiMSum: an error model and pipeline for analyzing deep mutational scanning data and diagnosing common experimental pathologies

Author(s): Andre J. Faure, Jörn M. Schmiedel, Pablo Baeza-Centurion, Ben Lehner
Published in: Genome Biology, Issue 21, 2021, ISSN 1474-760X
Publisher: Springer Science and Business Media LLC
DOI: 10.1186/s13059-020-02091-3

Neuronal perception of the social environment generates an inherited memory that controls the development and generation time of C. elegans

Author(s): Marcos Francisco Perez, Mehrnaz Shamalnasab, Alejandro Mata-Cabana, María Olmedo, Mirko Francesconi, Ben Lehner
Published in: Current Biology, 2021, ISSN 0960-9822
Publisher: Cell Press
DOI: 10.1016/j.cub.2021.07.031

Massively parallel genetic perturbation suggests the energetic structure of an amyloid-β transition state

Author(s): Anna Arutyunyan, Mireia Seuma, Andre J. Faure, Benedetta Bolognesi, Ben Lehner
Published in: Science Advances, Issue 11, 2025, ISSN 2375-2548
Publisher: American Association for the Advancement of Science (AAAS)
DOI: 10.1126/sciadv.adv1422

A small molecule stabilizer rescues the surface expression of nearly all missense variants in a GPCR

Author(s): Taylor L. Mighell, Ben Lehner
Published in: Nature Structural & Molecular Biology, Issue 32, 2025, Page(s) 2429-2440, ISSN 1545-9993
Publisher: Nature Publishing Group
DOI: 10.1038/s41594-025-01659-6

The energetic and allosteric landscape for KRAS inhibition

Author(s): Chenchun Weng, Andre J. Faure, Albert Escobedo, Ben Lehner
Published in: Nature, Issue 626, 2024, Page(s) 643-652, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-023-06954-0

Deep indel mutagenesis reveals the regulatory and modulatory architecture of alternative exon splicing

Author(s): Pablo Baeza-Centurión, Belén Miñana, Andre J. Faure, Mike Thompson, Sophie Bonnal, Gioia Quarantani, Joseph Clarke, Ben Lehner, Juan Valcárcel
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-025-62957-7

The allosteric landscape of the Src kinase

Author(s): Antoni Beltran, Mohsin M. Naqvi, Andre J. Faure, Ben Lehner
Published in: Science Advances, Issue 12, 2026, ISSN 2375-2548
Publisher: American Association for the Advancement of Science (AAAS)
DOI: 10.1126/sciadv.aea2726

The impact of rare germline variants on human somatic mutation processes

Author(s): Ben Lehner; Fran Supek; Mischan Vali Pour Jamnani
Published in: Crossref, Issue 1, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-31483-1

Mapping the energetic and allosteric landscapes of protein binding domains.

Author(s): Andre J. Faure; Júlia Domingo; Jörn M. Schmiedel; Cristina Hidalgo-Carcedo; Guillaume Diss; Ben Lehner
Published in: Crossref, Issue 1, 2022, ISSN 1476-4687
Publisher: Nature Research
DOI: 10.1038/s41586-022-04586-4

The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer’s disease mutations

Author(s): Mireia Seuma, Andre J Faure, Marta Badia, Ben Lehner, Benedetta Bolognesi
Published in: eLife, Issue 10, 2023, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/elife.63364

Site-saturation mutagenesis of 500 human protein domains

Author(s): Antoni Beltran, Xiang’er Jiang, Yue Shen, Ben Lehner
Published in: Nature, Issue 637, 2025, Page(s) 885-894, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-024-08370-4

SUNi mutagenesis: Scalable and uniform nicking for efficient generation of variant libraries

Author(s): Taylor L. Mighell, Ignasi Toledano, Ben Lehner
Published in: PLOS ONE, Issue 18, 2023, Page(s) e0288158, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0288158

An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation.

Author(s): Benedetta Bolognesi; Ben Lehner; Mireia Seuma
Published in: Crossref, Issue 1, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-34742-3

Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules

Author(s): Ignasi Toledano, Fran Supek, Ben Lehner
Published in: Nature Genetics, Issue 56, 2024, Page(s) 1914-1924, ISSN 1061-4036
Publisher: Nature Publishing Group
DOI: 10.1038/s41588-024-01878-5

MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis, and allostery from deep mutational scanning data

Author(s): Andre J. Faure, Ben Lehner
Published in: Genome Biology, Issue 25, 2024, ISSN 1474-760X
Publisher: Springer Science and Business Media LLC
DOI: 10.1186/s13059-024-03444-y

The genetic architecture of protein stability

Author(s): Andre J. Faure, Aina Martí-Aranda, Cristina Hidalgo-Carcedo, Antoni Beltran, Jörn M. Schmiedel, Ben Lehner
Published in: Nature, Issue 634, 2024, Page(s) 995-1003, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-024-07966-0

Genetics, energetics, and allostery in proteins with randomized cores and surfaces

Author(s): Albert Escobedo, Gesa Voigt, Andre J. Faure, Ben Lehner
Published in: Science, Issue 389, 2025, ISSN 0036-8075
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.adq3948

Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers.

Author(s): Park, Solip; Supek, Fran; Lehner, Ben; park
Published in: Nature Communications, Issue 1, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-27242-3

Dominance vs epistasis: the biophysical origins and plasticity of genetic interactions within and between alleles

Author(s): Xuan Xie, Xia Sun, Yuheng Wang, Ben Lehner, Xianghua Li
Published in: Nature Communications, Issue 14, 2023, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-023-41188-8

Massive experimental quantification allows interpretable deep learning of protein aggregation

Author(s): Mike Thompson, Mariano Martín, Trinidad Sanmartín Olmo, Chandana Rajesh, Peter K. Koo, Benedetta Bolognesi, Ben Lehner
Published in: Science Advances, Issue 11, 2025, ISSN 2375-2548
Publisher: American Association for the Advancement of Science (AAAS)
DOI: 10.1126/sciadv.adt5111

Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function

Author(s): Magdalena Topolska, Antoni Beltran, Ben Lehner
Published in: Nature Communications, Issue 16, 2025, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-025-57510-5