Evidence map›Paper›PMID 38719472›Full record

ArticleGenome research2024

A new framework for exploratory network mediator analysis in omics data.

Qingpo Cai, Yinghao Fu, Cheng Lyu, Zihe Wang, Shun Rao, Jessica A Alvarez, Yun Bai, Jian Kang, Tianwei Yu

Abstract read
In one paragraph

Article in Genome research, 2024. 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

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

9 authors.

Qingpo Cai *Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30322, USA.
Yinghao Fu *Shenzhen Research Institute of Big Data, School of Data Science, the Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong 518172, P.R. China.
Cheng Lyu *Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia 30322, USA.
Zihe WangShenzhen Research Institute of Big Data, School of Data Science, the Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong 518172, P.R. China.
Shun RaoShenzhen Research Institute of Big Data, School of Data Science, the Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong 518172, P.R. China.
Jessica A AlvarezDepartment of Medicine, Emory University, Atlanta, Georgia 30322, USA.
Yun BaiSchool of Medicine, the Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong 518172, P.R. China.
Jian KangDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA jiankang@umich.edu yutianwei@cuhk.edu.cn.
Tianwei YuShenzhen Research Institute of Big Data, School of Data Science, the Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen), Guangdong 518172, P.R. China; jiankang@umich.edu yutianwei@cuhk.edu.cn.

Funding

Statistical ICA Methods for Analysis & Integration of Multi-dimensional Data Diversity SupplementR01MH105561 · NIMH · EMORY UNIVERSITY · PI GUO, YING, KANG, JIAN · 2014 to 2024
$4.3M
Scalable Bayesian methods for big imaging data analysisR01DA048993 · NIDA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHNSON, TIMOTHY D, KANG, JIAN · 2020 to 2024
$1.6M
Bayesian Network Biomarker Selection in Metabolomics DataR01GM124061 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANG, JIAN · 2017 to 2020
$1.4M
NIDA NIH HHS R01 DA048993NIGMS NIH HHS R01 GM124061NIMH NIH HHS R01 MH105561
6 · The paper itself

Abstract

Omics methods are widely used in basic biology and translational medicine research. More and more omics data are collected to explain the impact of certain risk factors on clinical outcomes. To explain the mechanism of the risk factors, a core question is how to find the genes/proteins/metabolites that mediate their effects on the clinical outcome. Mediation analysis is a modeling framework to study the relationship between risk factors and pathological outcomes, via mediator variables. However, high-dimensional omics data are far more challenging than traditional data: (1) From tens of thousands of genes, can we overcome the curse of dimensionality to reliably select a set of mediators? (2) How do we ensure that the selected mediators are functionally consistent? (3) Many biological mechanisms contain nonlinear effects. How do we include nonlinear effects in the high-dimensional mediation analysis? (4) How do we consider multiple risk factors at the same time? To meet these challenges, we propose a new exploratory mediation analysis framework, medNet, which focuses on finding mediators through predictive modeling. We propose new definitions for predictive exposure, predictive mediator, and predictive network mediator, using a statistical hypothesis testing framework to identify predictive exposures and mediators. Additionally, two heuristic search algorithms are proposed to identify network mediators, essentially subnetworks in the genome-scale biological network that mediate the effects of single or multiple exposures. We applied medNet on a breast cancer data set and a metabolomics data set combined with food intake questionnaire data. It identified functionally consistent network mediators for the exposures' impact on the outcome, facilitating data interpretation.

Indexed as

Breast NeoplasmsAlgorithmsFemaleGene Regulatory NetworksGenomicsHumansMetabolomicsRisk Factors

Identifiers

PMID38719472
PMCPMC11146592

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.