Evidence map›Paper›PMID 39856048›Full record

ArticleNature communications2025

A multiscale functional map of somatic mutations in cancer integrating protein structure and network topology.

Yingying Zhang, Alden K Leung, Jin Joo Kang, Yu Sun, Guanxi Wu, Le Li, Jiayang Sun, Lily Cheng, Tian Qiu, Junke Zhang and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Yingying Zhang *Department of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.ORCID http://orcid.org/0000-0003-3819-5467
Alden K Leung *Department of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Jin Joo KangDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Yu SunDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.ORCID http://orcid.org/0000-0002-6635-9695
Guanxi WuCollege of Agriculture and Life Sciences, Cornell University, Ithaca, 14853, NY, USA.ORCID http://orcid.org/0009-0003-8111-9037
Le LiDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Jiayang SunDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Lily ChengDepartment of Science and Technology Studies, Cornell University, Ithaca, 14853, NY, USA.
Tian QiuSchool of Electrical and Computer Engineering, Cornell University, Ithaca, 14853, NY, USA.
Junke ZhangDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Shayne D WierbowskiDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.ORCID http://orcid.org/0000-0002-2595-2011
Shagun GuptaDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.ORCID http://orcid.org/0000-0002-4337-1413
James G BoothDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA.
Haiyuan YuDepartment of Computational Biology, Cornell University, Ithaca, 14853, NY, USA. haiyuan.yu@cornell.edu.ORCID http://orcid.org/0000-0001-7597-6049

Funding

Integrated high-throughput functional assays to identify ulcerative colitis causal risk variantsR01DK115398 · NIDDK · CORNELL UNIVERSITY · PI KLEIN, ROBERT J., YU, HAIYUAN · 2018 to 2022
$3.3M
Quantifying molecular consequences of human missense variants with large-scale interactome perturbation studiesR01GM125639 · NIGMS · CORNELL UNIVERSITY · PI ALEXOV, EMIL GEORGIEV, CLARK, ANDREW G · 2018 to 2021
$2.6M
Towards a comprehensive multiscale 3D human interactome networkR01GM124559 · NIGMS · CORNELL UNIVERSITY · PI YU, HAIYUAN · 2017 to 2020
$1.5M
Deep learning based 3D network biology knowledge portal for precision oncologyU01CA294154 · NCI · CORNELL UNIVERSITY · PI Feixiong Cheng, Haiyuan Yu · 2025 to 2026
$814k
NCI NIH HHS U01 CA294154NIDDK NIH HHS R01 DK115398NIGMS NIH HHS R01 GM124559NIGMS NIH HHS R01 GM125639Simons Foundation 575547
6 · The paper itself

Abstract

A major goal of cancer biology is to understand the mechanisms driven by somatically acquired mutations. Two distinct methodologies-one analyzing mutation clustering within protein sequences and 3D structures, the other leveraging protein-protein interaction network topology-offer complementary strengths. We present NetFlow3D, a unified, end-to-end 3D structurally-informed protein interaction network propagation framework that maps the multiscale mechanistic effects of mutations. Built upon the Human Protein Structurome, which incorporates the 3D structures of every protein and the binding interfaces of all known protein interactions, NetFlow3D integrates atomic, residue, protein and network-level information: It clusters mutations on 3D protein structures to identify driver mutations and propagates their impacts anisotropically across the protein interaction network, guided by the involved interaction interfaces, to reveal systems-level impacts. Applied to 33 cancer types, NetFlow3D identifies 2 times more 3D clusters and incorporates 8 times more proteins in significantly interconnected network modules compared to traditional methods.

Indexed as

MutationNeoplasmsProtein Interaction MappingProtein Interaction MapsComputational BiologyHumansProtein Conformation

Identifiers

PMID39856048
PMCPMC11760531

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.