Evidence map›Paper›PMID 40781375›Full record

ReviewMolecular systems biology2025

Variant scoring tools for deep mutational scanning.

Hasan Çubuk, Xinyi Jin, Belinda Phipson, Joseph A Marsh, Alan F Rubin

Abstract readReview
In one paragraph

Review in Molecular systems biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Hasan Çubuk *MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.ORCID http://orcid.org/0000-0001-6203-4132
Xinyi Jin *Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0002-2222-0958
Belinda PhipsonBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.ORCID http://orcid.org/0000-0002-1711-7454
Joseph A MarshMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. joseph.marsh@ed.ac.uk.ORCID http://orcid.org/0000-0003-4132-0628
Alan F RubinBioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. alan.rubin@wehi.edu.au.ORCID http://orcid.org/0000-0003-1474-605X

Funding

Technology to understand genetic variant effects in contextRM1HG010461 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Bruce Colston Trapnell · 2019 to 2026
$18.9M
The Center for Actionable Variant Analysis; measuring variant function at scaleUM1HG011969 · NHGRI · UNIVERSITY OF WASHINGTON · PI Douglas M Fowler, Lea Starita · 2021 to 2026
$9.9M
EC | European Research Council (ERC) 101001169Federal Government | DHAC | National Health and Medical Research Council (NHMRC) GNT2025641HHS | NIH | National Human Genome Research Institute (NHGRI) RM1HG010461HHS | NIH | National Human Genome Research Institute (NHGRI) UM1HG011969NHGRI NIH HHS RM1 HG010461NHGRI NIH HHS UM1 HG011969UKRI | Medical Research Council (MRC) MC_UU_00035/9
6 · The paper itself

Abstract

Deep mutational scanning (DMS) can systematically assess the effects of thousands of genetic variants in a single assay, providing insights into protein function, evolution, host-pathogen interactions, and clinical impacts. Accurate scoring of variant effects is crucial, yet the diversity of tools and experimental designs contributes considerable heterogeneity that complicates data analysis. Here, we review and compare 12 computational tools for processing DMS sequencing data and scoring variant effects. We systematically outline each tool's statistical approaches, supported experimental designs, input/output requirements, software implementation, visualisation capabilities, and key assumptions. By highlighting the strengths and limitations of these tools, we hope to guide researchers in selecting methods appropriate for their specific experiments. Furthermore, we discuss current challenges, including the need for standardised analysis protocols and sustainable software maintenance, as well as opportunities for future methods development. Ultimately, this review seeks to advance the application and adoption of DMS, facilitating deeper biological understanding and improved clinical translation.

Indexed as

Computational BiologyDNA Mutational AnalysisHigh-Throughput Nucleotide SequencingGenetic VariationHumansMutationSoftwareBioinformaticsDeep Mutational ScanningFunctional GenomicsMultiplexed Assays of Variant EffectSoftware

Identifiers

PMID40781375
PMCPMC12494760

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.