Dataset Information

Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes.

ABSTRACT: Maternal-fetal genotype incompatibility (MFGI) is increasingly reported to influence human diseases, especially pregnancy-related complications. In practice, it is challenging to identify the ideal incompatibility model for analysis, since the true MFGI mechanism is generally unknown. The underlying MFGI mechanism for different genetic variants can vary, and to use a single incompatibility model for all circumstances would cause power loss in testing MFGI.In this article, we propose a practical 2-step procedure that incorporates a model selection strategy based on an entropy measurement to select the most appropriate MFGI model represented by data and test the significance of the MFGI effect using the chosen model within the generalized linear regression framework.Our simulation studies show that the proposed two-step procedure controls the type I error rate and increase the testing power under various scenarios. In a real data application, our analysis reveals genes having an MFGI effect, which may not be detected with a non-model selection counterpart.

SUBMITTER: Li S

PROVIDER: S-EPMC4057811 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes.

Li Shaoyu S Cui Yuehua Y Romero Roberto R

BMC genetics 20140610

<h4>Background</h4>Maternal-fetal genotype incompatibility (MFGI) is increasingly reported to influence human diseases, especially pregnancy-related complications. In practice, it is challenging to identify the ideal incompatibility model for analysis, since the true MFGI mechanism is generally unknown. The underlying MFGI mechanism for different genetic variants can vary, and to use a single incompatibility model for all circumstances would cause power loss in testing MFGI.<h4>Results</h4>In th ...[more]

PMID: 24916189

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Project description:BackgroundGlobally, preterm birth remains the leading cause of death in children younger than 5 years old. Spontaneous preterm birth is comprised of two events that may or may not occur simultaneously: preterm labor and preterm prelabor rupture of membranes (PPROM). To further explore the concept that spontaneous preterm birth can result from the initializing of two separate but overlapping pathological events, we compared fetal membrane tissue from preterm labor deliveries to fetal tissue from preterm labor with PPROM deliveries. We hypothesized that the fetal membrane tissue from preterm labor with PPROM cases will have an RNA-seq profile divergent from the fetal membrane tissue from preterm labor controls.MethodsChorioamnion, separated into amnion and chorion, was collected from eight gestationally age-matched cases and controls within 15 min of birth, and analyzed using RNA sequencing. Pathway enrichment analyses and functional annotations of differentially expressed genes were performed using KEGG and Gene Ontogeny Pathway enrichment analyses.ResultsA total of 1466 genes were differentially expressed in the amnion, and 484 genes were differentially expressed in the chorion (log2 fold change > 1, FDR < 0.05) in cases (preterm labor with PPROM), versus controls (preterm labor only). In the amnion, the most significantly enriched (FDR < 0.01) KEGG pathway among down-regulated genes was the extracellular matrix receptor interaction pathway. Seven of the most significantly enriched pathways were comprised of multiple genes from the COL family, including COL1A, COL3A1, COL4A4, and COL4A6. In the chorion, the most significantly enriched KEGG pathways in up-regulated genes were chemokine, NOD receptor, Toll-like receptor, and cytokine-cytokine receptor signaling pathways. Similarly, KEGG pathway enrichment analysis for up-regulated genes in the amnion included three inflammatory pathways: cytokine-cytokine interaction, TNF signaling and the CXCL family. Six genes were significantly up regulated in chorionic tissue discriminated between cases (preterm labor with PPROM) and controls (preterm labor only) including GBP5, CXCL9, ALPL, S100A8, CASP5 and MMP25.ConclusionsIn our study, transcriptome analysis of preterm fetal membranes revealed distinct differentially expressed genes for PPROM, separate from preterm labor. This study is the first to report transcriptome data that reflects the individual pathophysiology of amnion and chorion tissue from PPROM deliveries.

Project description:ObjectiveTo evaluate maternal serum C-reactive protein (CRP) concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) in relation to the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).MethodsTwo hundred and eighty-seven women with singleton pregnancies complicated by PPROM between 2014 and 2016 were included in this study. Maternal blood and amniotic fluid samples were collected at the time of admission. Maternal serum CRP concentration was measured using a high-sensitivity immunoturbidimetric assay. Interleukin-6 (IL-6) concentration was measured using a point-of-care test. MIAC was diagnosed based on a positive polymerase chain reaction result for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and for the 16S rRNA gene. IAI was characterized by an amniotic fluid IL-6 concentration of ≥ 745 pg/mL.ResultWomen with MIAC and IAI had higher maternal serum CRP concentrations than did women without (with MIAC: median 6.9 mg/L vs. without MIAC: median 4.9 mg/L; p = 0.02; with IAI: median 8.6 mg/L vs. without IAI: median 4.7 mg/L; p < 0.0001). When women were split into four subgroups based on the presence of MIAC and/or IAI, women with the presence of both MIAC and IAI had higher maternal serum CRP than did women with IAI alone, with MIAC alone, and women without MIAC and IAI (both MIAC and IAI: median: 13.1 mg/L; IAI alone: 6.0 mg/L; MIAC alone: 3.9 mg/L; and without MIAC and IAI: median 4.8 mg/L; p < 0.0001). The maternal serum CRP cutoff value of 17.5 mg/L was the best level to identify the presence of both MIAC and IAI, with sensitivity of 47%, specificity of 96%, positive predictive value of 42%, negative predictive value of 96%, and the positive likelihood ratio of 10.9.ConclusionThe presence of both MIAC and IAI was associated with the highest maternal serum CRP concentrations. Maternal serum CRP concentration in women with PPROM at the time of admission can rule out the presence of the combined condition of both MIAC and IAI, therefore, it may serve as a non-invasive screening tool to distinguish between women with PPROM who are at high or at low risk for the presence of both MIAC and IAI.

Dataset Information

Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes.

Publications

Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes.

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