Evidence map›Paper›PMID 35669036›Full record

ArticleiScience2022

Modeling mutational effects on biochemical phenotypes using convolutional neural networks: application to SARS-CoV-2.

Bo Wang, Eric R Gamazon

Open access · goldAbstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.3field-weighted citation impact, top 45% of its field
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

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Neural networks to learn protein sequence-function relationships from deep mutational scanning data.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Bo WangDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Eric R GamazonDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
University of Cambridge · GBVanderbilt University Medical Center · US

Funding

Haplotype-aware models of gene and isoform expression with application to genetic studies of disease in diverse populationsR01GM140287 · NIGMS · SEATTLE CHILDREN'S HOSPITAL · PI GAMAZON, ERIC R, MOHAMMADI, PEJMAN · 2021 to 2024
$2.8M
Functional Genomics: A Phenome-wide SurveyR35HG010718 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAMAZON, ERIC R · 2019 to 2023
$2.2M
Advancing Multi-Omics and Electronic Health Records Computational MethodologiesR01HG011138 · NHGRI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAMAZON, ERIC R · 2020 to 2024
$1.6M
Advancing drug repositioning and development for Alzheimer's Disease using functional genomics and computational phenomicsR56AG068026 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAMAZON, ERIC R · 2021 to 2022
$1.5M
NHGRI NIH HHS R01 HG011138NHGRI NIH HHS R35 HG010718NIA NIH HHS R56 AG068026NIGMS NIH HHS R01 GM140287
6 · The paper itself

Abstract

Deep mutational scanning (DMS) experiments have been performed on SARS-CoV-2's spike receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) zinc-binding peptidase domain-both central players in viral infection and evolution and antibody evasion-quantifying how mutations impact biochemical phenotypes. We modeled biochemical phenotypes from massively parallel assays, using neural networks trained on protein sequence mutations in the virus and human host. Neural networks were significantly predictive of binding affinity, protein expression, and antibody escape, learning complex interactions and higher-order features that are difficult to capture with conventional methods from structural biology. Integrating the physicochemical properties of amino acids, such as hydrophobicity and long-range non-bonded energy per atom, significantly improved prediction (empirical p < 0.01). We observed concordance of the neural network predictions with molecular dynamics (multiple 500 ns or 1 μs all-atom) simulations of the spike protein-ACE2 interface, with critical implications for the use of deep learning to dissect molecular mechanisms.

Indexed as

Computational intelligenceComputational molecular modelingHealth sciences

Identifiers

PMID35669036
PMCPMC9159778
OpenAlexW4281620993

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.