Methylation differences reveal heterogeneity in preterm pathophysiology: results from bipartite network analyses

Bhavnani, Suresh K.; Dang, Bryant; Kilaru, Varun; Caro, Maria; Visweswaran, Shyam; Saade, George R.; Smith, Alicia K.; Menon, Ramkumar

doi:10.1515/jpm-2017-0126

Cited by 13 publications

(12 citation statements)

References 54 publications

(64 reference statements)

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“…4. For prematurity, two different aberrant DNA hypomethylation patterns suggest a heterogeneous pathophysiology [103]. With 6-19-week cervical DNA, increased methylation of prostaglandin E receptor 2 gene (PTGER2) showed longer gestations, while repetitive long interspersed nuclear element-1 Homo sapiens-specific (LINE 1-HS) were shorter.…”

Section: With Early Pregnancy Losses Dnmt 1 Expression and Glob-mentioning

confidence: 99%

An epigenetic association of malformations, adverse reproductive outcomes, and fetal origins hypothesis related effects

Lubinsky

2018

J Assist Reprod Genet

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VACTERL, the prototype for associated congenital anomalies, also has connections with functional issues such as pregnancy losses, prematurity, growth delays, perinatal difficulties, and parental subfertility. This segues into a broader association with similar connections even in the absence of malformations. DNA methylation disturbances in the ovum are a likely cause, with epigenetic links to individual components and to folate effects before conception, explaining diverse fetal and placental findings and providing a link to fetal origin hypothesis-related effects. The association encompasses the following: (1) Pre- and periconceptual effects, with frequent fertility issues and occasional imprinting disorders. (2) Early malformations. (3) Adverse pregnancy outcomes (APOs), as above. (4) Developmental destabilization that resolves soon after birth. This potentiates other causes of association findings, introducing multiple confounders. (5) Long-term fetal origins hypothesis-related risks. The other findings are exceptional when the same malformations have Mendelian origins, supporting a distinct pathogenesis. Expressions are facilitated by one-carbon metabolic issues, maternal and fetal stress, and decreased embryo size. This may be one of the commonest causes of adverse reproductive outcomes, but multifactorial findings, variable onsets and phenotypes, and interactions with multiple confounders make recognition difficult. This association supports VACTERL as a continuum that includes isolated malformations, extends the fetal origins hypothesis, explains adverse effects linked to maternal obesity, and suggests possible interventions.

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Section: With Early Pregnancy Losses Dnmt 1 Expression and Glob-mentioning

confidence: 99%

An epigenetic association of malformations, adverse reproductive outcomes, and fetal origins hypothesis related effects

Lubinsky

2018

J Assist Reprod Genet

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“…Study selection 999 references were imported from the search. Of the 74 abstracts that met initial inclusion criteria, the fulltext review led to inclusion of 16 studies [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] that drew from 13 birth cohorts and exclusion of 58 studies (Figure 1 & Table 1). Among excluded studies, two were excluded because they were transcriptomic [45] and metabolomic [46] studies.…”

Section: Resultsmentioning

confidence: 99%

Racial and Ethnic Representation in Epigenomic Studies of Preterm Birth: A Systematic Review

et al. 2020

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Aim: We conducted a systematic review evaluating race/ethnicity representation in DNA methylomic studies of preterm birth. Data sources: PubMed, EMBASE, CINHAL, Scopus and relevant citations from 1 January 2000 to 30 June 2019. Study appraisal & synthesis methods: Two authors independently identified abstracts comparing DNA methylomic differences between term and preterm births that included race/ethnicity data. Results: 16 studies were included. Black and non-Hispanic Black deliveries were well represented (28%). However, large studies originating from more than 95% White populations were excluded due to unreported race/ethnicity data. Most studies were cross-sectional, allowing for reverse causation. Most studies were also racially/ethnically homogeneous, preventing direct comparison of DNA methylomic differences across race/ethnicities. Conclusion: In DNA methylomic studies, Black women and infants were well represented. However, the literature has limitations and precludes drawing definitive conclusions.

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“…The proteome data sets were previously described ( 19 ). Log-transformed proteome data sets were subjected to bipartite network analysis and visualization ( 49 ) using the following steps: (i) feature selection to identify which protein spots were univariably significant (after FDR correction) between different comparison groups; (ii) bipartite modularity maximization ( 50 ) to identify biclusters of patients and protein spots, with testing of significance through comparison to biclustering generated from 1,000 permutations of the data; and (iii) enrichment analysis using χ 2 to determine if there was a significantly different proportion of phenotypes in each bicluster compared to the rest of the data.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Performance of Peripheral Blood Biomarkers in Identifying Seropositive Individuals at Risk of Developing Clinically Symptomatic Chagas Cardiomyopathy

et al. 2021

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Methylation differences reveal heterogeneity in preterm pathophysiology: results from bipartite network analyses

Cited by 13 publications

References 54 publications

An epigenetic association of malformations, adverse reproductive outcomes, and fetal origins hypothesis related effects

An epigenetic association of malformations, adverse reproductive outcomes, and fetal origins hypothesis related effects

Racial and Ethnic Representation in Epigenomic Studies of Preterm Birth: A Systematic Review

Prognostic Performance of Peripheral Blood Biomarkers in Identifying Seropositive Individuals at Risk of Developing Clinically Symptomatic Chagas Cardiomyopathy

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