Biomarkers of Necrotizing Enterocolitis in the Era of Machine Learning and Omics

Overview

Journal Semin Perinatol

Specialty Gynecology & Obstetrics

Date 2023 Jan 5

PMID 36604292

Authors

Tyler Leiva

Shiloh Lueschow

Kathryn Burge

Christa Devette

Steven McElroy

Hala Chaaban

Affiliations

Soon will be listed here.

Abstract

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in preterm infants. Despite decades of research in NEC, no reliable biomarkers can accurately diagnose NEC or predict patient prognosis. The recent emergence of multi-omics could potentially shift NEC biomarker discovery, particularly when evaluated using systems biology techniques. Furthermore, the use of machine learning and artificial intelligence in analyzing this 'big data' could enable novel interpretations of NEC subtypes, disease progression, and potential therapeutic targets, allowing for integration with personalized medicine approaches. In this review, we evaluate studies using omics technologies and machine learning in the diagnosis of NEC. Future implications and challenges inherent to the field are also discussed.

Citing Articles

Detection of an intestinal cell DNA methylation signature in blood samples from neonates with necrotizing enterocolitis.

Frazer L, Chu T, Shaw P, Boufford C, Naief L, Ednie M Epigenomics. 2025; 17(4):235-245.

PMID: 39894787 PMC: 11853613. DOI: 10.1080/17501911.2025.2459552.

CCL3 as a novel biomarker in the diagnosis of necrotizing enterocolitis.

Zeng L, Liu W, Li Y, Song Z, Li H, Yin Y BMC Pediatr. 2024; 24(1):843.

PMID: 39732631 PMC: 11681690. DOI: 10.1186/s12887-024-05307-8.

Prevention of Inflammatory Disorders in the Preterm Neonate: An Update with a Special Focus on Bronchopulmonary Dysplasia.

Glaser K, Jensen E, Wright C Neonatology. 2024; 121(5):636-645.

PMID: 38870912 PMC: 11444906. DOI: 10.1159/000539303.

References

. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69(3):89-95. DOI: 10.1067/mcp.2001.113989. View

Fortino V, Wisgrill L, Werner P, Suomela S, Linder N, Jalonen E . Machine-learning-driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis. Proc Natl Acad Sci U S A. 2020; 117(52):33474-33485. PMC: 7776829. DOI: 10.1073/pnas.2009192117. View

Wilcock A, Begley P, Stevens A, Whatmore A, Victor S . The metabolomics of necrotising enterocolitis in preterm babies: an exploratory study. J Matern Fetal Neonatal Med. 2015; 29(5):758-62. DOI: 10.3109/14767058.2015.1017462. View

Zhou W, Cai Z, Liu J, Wang D, Ju H, Xu R . Circular RNA: metabolism, functions and interactions with proteins. Mol Cancer. 2020; 19(1):172. PMC: 7734744. DOI: 10.1186/s12943-020-01286-3. View

Rusconi B, Jiang X, Sidhu R, Ory D, Warner B, Tarr P . Gut Sphingolipid Composition as a Prelude to Necrotizing Enterocolitis. Sci Rep. 2018; 8(1):10984. PMC: 6054655. DOI: 10.1038/s41598-018-28862-4. View

Martin C . Definitions of necrotizing enterocolitis: What are we defining and is machine learning the answer?. Pediatr Res. 2021; 91(3):488-489. DOI: 10.1038/s41390-021-01687-0. View

Vernocchi P, Del Chierico F, Putignani L . Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health. Front Microbiol. 2016; 7:1144. PMC: 4960240. DOI: 10.3389/fmicb.2016.01144. View

Yu W, Haque I, Venkatraman A, Menden H, Mabry S, Roy B . SIGIRR Mutation in Human Necrotizing Enterocolitis (NEC) Disrupts STAT3-Dependent microRNA Expression in Neonatal Gut. Cell Mol Gastroenterol Hepatol. 2021; 13(2):425-440. PMC: 8688179. DOI: 10.1016/j.jcmgh.2021.09.009. View

Banyasz I, Bokodi G, Vasarhelyi B, Treszl A, Derzbach L, Szabo A . Genetic polymorphisms for vascular endothelial growth factor in perinatal complications. Eur Cytokine Netw. 2007; 17(4):266-70. View

10.

Lin Y, Salleb-Aouissi A, Hooven T . Interpretable prediction of necrotizing enterocolitis from machine learning analysis of premature infant stool microbiota. BMC Bioinformatics. 2022; 23(1):104. PMC: 8953333. DOI: 10.1186/s12859-022-04618-w. View

11.

Xie Y, Meng W, Li R, Wang Y, Qian X, Chan C . Early lung cancer diagnostic biomarker discovery by machine learning methods. Transl Oncol. 2020; 14(1):100907. PMC: 7683339. DOI: 10.1016/j.tranon.2020.100907. View

12.

Carlisle E, Poroyko V, Caplan M, Alverdy J, Morowitz M, Liu D . Murine gut microbiota and transcriptome are diet dependent. Ann Surg. 2012; 257(2):287-94. DOI: 10.1097/SLA.0b013e318262a6a6. View

13.

Noorbakhsh-Sabet N, Zand R, Zhang Y, Abedi V . Artificial Intelligence Transforms the Future of Health Care. Am J Med. 2019; 132(7):795-801. PMC: 6669105. DOI: 10.1016/j.amjmed.2019.01.017. View

14.

Eaton S, Rees C, Hall N . Current research in necrotizing enterocolitis. Early Hum Dev. 2016; 97:33-9. DOI: 10.1016/j.earlhumdev.2016.01.013. View

15.

Sampath V, Menden H, Helbling D, Li K, Gastonguay A, Ramchandran R . SIGIRR genetic variants in premature infants with necrotizing enterocolitis. Pediatrics. 2015; 135(6):e1530-4. PMC: 4444800. DOI: 10.1542/peds.2014-3386. View

16.

Grapov D, Fahrmann J, Wanichthanarak K, Khoomrung S . Rise of Deep Learning for Genomic, Proteomic, and Metabolomic Data Integration in Precision Medicine. OMICS. 2018; 22(10):630-636. PMC: 6207407. DOI: 10.1089/omi.2018.0097. View

17.

Zwiers A, van Wanrooij R, Dieckman T, Nijeboer P, Kraal G, Bouma G . Celiac disease associated SNP rs17810546 is located in a gene silencing region. Gene. 2019; 726:144165. DOI: 10.1016/j.gene.2019.144165. View

18.

Prencipe G, Azzari C, Moriondo M, DeVito R, Inglese R, Pezzullo M . Association between mannose-binding lectin gene polymorphisms and necrotizing enterocolitis in preterm infants. J Pediatr Gastroenterol Nutr. 2012; 55(2):160-5. DOI: 10.1097/MPG.0b013e31824e5f7a. View

19.

Gao X, Ma F, Hao H, Dai Y, Liu W, Xiao X . Association of VEGFA polymorphisms with necrotizing enterocolitis in Chinese Han population. Pediatr Neonatol. 2018; 60(2):129-134. DOI: 10.1016/j.pedneo.2018.07.002. View

20.

Chaaban H, Markel T, Canvasser J, Good M . Biobanking for necrotizing enterocolitis: Needs and standards. J Pediatr Surg. 2019; 55(7):1276-1279. PMC: 6842670. DOI: 10.1016/j.jpedsurg.2019.05.002. View