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Machine-learning-based integrative -'omics analyses reveal immunologic and metabolic dysregulation in environmental enteric dysfunction.

Authors :
Zulqarnain F
Zhao X
Setchell KDR
Sharma Y
Fernandes P
Srivastava S
Shrivastava A
Ehsan L
Jain V
Raghavan S
Moskaluk C
Haberman Y
Denson LA
Mehta K
Iqbal NT
Rahman N
Sadiq K
Ahmad Z
Idress R
Iqbal J
Ahmed S
Hotwani A
Umrani F
Amadi B
Kelly P
Brown DE
Moore SR
Ali SA
Syed S
Source :
IScience [iScience] 2024 May 17; Vol. 27 (6), pp. 110013. Date of Electronic Publication: 2024 May 17 (Print Publication: 2024).
Publication Year :
2024

Abstract

Environmental enteric dysfunction (EED) is a subclinical enteropathy challenging to diagnose due to an overlap of tissue features with other inflammatory enteropathies. EED subjects ( n  = 52) from Pakistan, controls ( n  = 25), and a validation EED cohort ( n  = 30) from Zambia were used to develop a machine-learning-based image analysis classification model. We extracted histologic feature representations from the Pakistan EED model and correlated them to transcriptomics and clinical biomarkers. In-silico metabolic network modeling was used to characterize alterations in metabolic flux between EED and controls and validated using untargeted lipidomics. Genes encoding beta-ureidopropionase, CYP4F3, and epoxide hydrolase 1 correlated to numerous tissue feature representations. Fatty acid and glycerophospholipid metabolism-related reactions showed altered flux. Increased phosphatidylcholine, lysophosphatidylcholine (LPC), and ether-linked LPCs, and decreased ester-linked LPCs were observed in the duodenal lipidome of Pakistan EED subjects, while plasma levels of glycine-conjugated bile acids were significantly increased. Together, these findings elucidate a multi-omic signature of EED.<br />Competing Interests: KDRS has equity in Asklepion Pharmaceuticals and is a consultant to Travere Therapeutics and Mirum Pharmaceuticals. All the other authors have no conflicts of interest to disclose.<br /> (© 2024 The Authors.)

Details

Language :
English
ISSN :
2589-0042
Volume :
27
Issue :
6
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
38868190
Full Text :
https://doi.org/10.1016/j.isci.2024.110013