Evidence map›Paper›PMID 42378448›Full record

ArticleBioinformatics (Oxford, England)2026

Sparse CCA-based mediation analysis with high-dimensional exposures and mediators.

Xincheng Li, Maiying Kong, Matthew Ryan Smith, Yongliang Liang, Sami Teeny, Vilinh T Ly, Young-Mi Go, Niharika Samala, Dean P Jones, Jianzhu Luo and 10 more

Abstract read
In one paragraph

Article in Bioinformatics (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

20 authors.

Xincheng LiDepartment of Statistics and Data Science, Northwestern University, Evanston, IL 60208, United States.
Maiying KongDepartment of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, United States.
Matthew Ryan SmithVA Healthcare System of Atlanta, Decatur, GA 30033, United States.
Yongliang LiangDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.
Sami TeenyDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.
Vilinh T LyDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.
Young-Mi GoDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.ORCID 0009-0005-0211-177X
Niharika SamalaSchool of Medicine, Indiana University, Indianapolis, IN 46202, United States.
Dean P JonesDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States.
Jianzhu LuoSchool of Medicine, University of Louisville, Louisville, KY 40202, United States.
Walter H WatsonSchool of Medicine, University of Louisville, Louisville, KY 40202, United States.
Craig J McClainSchool of Medicine, University of Louisville, Louisville, KY 40202, United States.
Vatsalya VatsalyaSchool of Medicine, University of Louisville, Louisville, KY 40202, United States.
Gyongyi SzaboBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
Srinivasan DasarathyCleveland Clinic, Cleveland, OH 44195, United States.
Mack MitchellUniversity of Texas Southwestern Medical Center, Dallas, TX 75390, United States.
Laura E NagyCleveland Clinic, Cleveland, OH 44195, United States.
Bruce BartonDepartment of Population and Quantitative Health Sciences, University of Massachusetts, Worcester, MA 01655, United States.ORCID 0000-0001-7878-8895
Matthew C CaveSchool of Medicine, University of Louisville, Louisville, KY 40202, United States.
Hongmei JiangDepartment of Statistics and Data Science, Northwestern University, Evanston, IL 60208, United States.ORCID 0000-0003-2286-2544

Funding

Pilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI William Michael Caudle · 2013 to 2026
$22.6M
Environmental Liver DiseaseR35ES028373 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2017 to 2024
$4.0M
RNA modifications in apolipoprotein regulation by environmental exposuresR01ES036210 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C, KLINGE, CAROLYN M. · 2025 to 2025
$3.1M
Exposome and Precision Medicine in NAFLDR01ES032189 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2020 to 2022
$1.9M
Summer Environmental Health Sciences Training ProgramT35ES014559 · NIEHS · UNIVERSITY OF LOUISVILLE · PI Matthew C Cave, Daniel Joseph Conklin · 2006 to 2026
$751k
Optimizing a human relevant mouse model to study adverse health effects of PFASR21ES035475 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SCHLEZINGER, JENNIFER J · 2024 to 2025
$468k
NIEHS NIH HHS P30ES019776NIEHS NIH HHS P30ES302883NIEHS NIH HHS R01ES032189NIEHS NIH HHS R01ES036210NIEHS NIH HHS R21ES032189NIEHS NIH HHS R21ES035475NIEHS NIH HHS R35ES028373NIEHS NIH HHS T35ES014559the National Institute of General Medical Sciences P20GM113226the National Institute of General Medical Sciences P20GM135004the National Institute of General Medical Sciences P20GM155899U.S. Department of Veterans Affairs 1IK2BX005913-01A2
6 · The paper itself

Abstract

motivationMediation analysis plays a crucial role in understanding how exposure variables influence health outcomes via intermediate variables, or mediators, in environmental studies. When analysing a large number of environmental exposures, such as chemical mixtures or pollutants, together with multiple potential mediators such as metabolites, advanced methodologies are necessary to accurately separate direct and indirect effects. This paper proposes a novel mediation analysis method based on Sparse Canonical Correlation Analysis (SCCA), designed specifically for settings where both exposures and mediators are high-dimensional. The effectiveness of the proposed method is evaluated through simulation studies and an application to real-world data.

resultsThe proposed SCCA-based mediation framework improved identification of relevant mediators and pathways in simulation studies, particularly in high-dimensional and noisy settings. The two-step screening extension further enhanced feature selection while maintaining stable estimation. In the real-data application, the method identified interpretable exposure-metabolite pathways associated with MELD score, with several pathways showing moderate selection stability and robustness to potential unmeasured confounding. AVAILABILITY: The R code for implementing the proposed method and the simulation studies is available at https://github.com/MaggieLi2001/HDM-SCCA2.

Indexed as

Computational BiologyEnvironmental ExposureMediation AnalysisAlgorithmsComputer SimulationHumans

Identifiers

PMID42378448
PMCPMC13384060

What Socratic holds

Textmetadata
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 Socratic graph.