An Integrative Analysis of Preeclampsia Based on the Construction of an Extended Composite Network Featuring Protein-Protein Physical Interactions and Transcriptional Relationships

Vaiman, Daniel; Miralles, Francisco

doi:10.1371/journal.pone.0165849

Cited by 16 publications

(9 citation statements)

References 78 publications

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“…It is unclear if the reduction in CLDN1 expression is causative or the result of repression due to increased levels of cytokines at the initiation of parturition. A recent meta-analysis of pre-eclampsia [ 46 ] demonstrated that CLDN1 was also downregulated suggesting a potential underlying mechanism to both idiopathic spontaneous and medically induced pre-eclampsia (PE) preterm birth.…”

Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of human placentae at term and preterm delivery†

Paquette

Brockway

Price

et al. 2017

Biology of Reproduction

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Preterm birth affects 1 out of every 10 infants in the United States, resulting in substantial neonatal morbidity and mortality. Currently, there are few predictive markers and few treatment options to prevent preterm birth. A healthy, functioning placenta is essential to positive pregnancy outcomes. Previous studies have suggested that placental pathology may play a role in preterm birth etiology. Therefore, we tested the hypothesis that preterm placentae may exhibit unique transcriptomic signatures compared to term samples reflective of their abnormal biology leading to this adverse outcome. We aggregated publicly available placental villous microarray data to generate a preterm and term sample dataset (n = 133, 55 preterm placentae and 78 normal term placentae). We identified differentially expressed genes using the linear regression for microarray (LIMMA) package and identified perturbations in known biological networks using Differential Rank Conservation (DIRAC). We identified 129 significantly differentially expressed genes between term and preterm placenta with 96 genes upregulated and 33 genes downregulated (P-value <0.05). Significant changes in gene expression in molecular networks related to Tumor Protein 53 and phosphatidylinositol signaling were identified using DIRAC. We have aggregated a uniformly normalized transcriptomic dataset and have identified novel and established genes and pathways associated with developmental regulation of the placenta and potential preterm birth pathology. These analyses provide a community resource to integrate with other high-dimensional datasets for additional insights in normal placental development and its disruption.

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Section: Discussionmentioning

confidence: 99%

Comparative transcriptomic analysis of human placentae at term and preterm delivery†

Paquette

Brockway

Price

et al. 2017

Biology of Reproduction

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“…A ausência de valores específicos do exame não impediu de verificar a associação com o desfecho, uma vez que não há relação entre a quantidade exata de proteína na urina, e, sim, sua ausência ou presença (17) . O ganho de peso e a obesidade foram significativos no 3º trimestre gestacional.…”

Section: Iresultadosunclassified

Características Definidoras E Fatores Associados À Ocorrência Das Síndromes Hipertensivas Gestacionais*

Sbardelotto

Pitilin

Schirmer³

et al. 2018

Cogitare Enferm.

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RESUMO: Objetivo: identificar as características definidoras e os fatores relacionados em Síndromes Hipertensivas Gestacionais. Método: estudo longitudinal, retrospectivo, realizado no centro de saúde de pré-natal de alto risco, num município do oeste catarinense em 2016. Como critérios de inclusão adotou-se: gestação única, que não tenha resultado em aborto ou óbito fetal, a data da última menstruação entre janeiro a dezembro de 2015, e a presença de diagnóstico da síndrome. Para a análise dos dados foi utilizado o software SPSS, versão 20.0. Resultados: foram analisados 90 prontuários, sendo reveladas as características definidoras dos diagnósticos pela elevação da pressão arterial e a presença de proteinúria. Os fatores relacionados foram: idade materna, ganho de peso, índice de massa corporal, antecedentes de doenças hipertensivas, número de consultas pré-natal e o uso de medicação anti-hipertensiva. Conclusão: identificou quais características predizem com maior exatidão a ocorrência do diagnóstico investigado, e a redução das formas graves da doença. DESCRITORES: Saúde da mulher; Hipertensão induzida pela gravidez; Perfil de saúde; Cuidado pré-natal. DEFINING CHARACTERISTICS AND FACTORS ASSOCIATED WITH THE OCCURRENCE OF GESTATIONAL HYPERTENSIVE SYNDROMESABSTRACT: Objective: to identify the defining characteristics and related factors of Gestational Hypertensive Syndromes. Method: longitudinal retrospective study performed at a high-risk prenatal health center in a city in the west of Santa Catarina in 2016. The inclusion criteria were singleton pregnancy that did not result in miscarriage of intrauterine fetal death, date of last menstrual period between January and December 2015 and diagnosis of Gestational Hypertensive Syndrome. SPSS software, version 20.0 was used in data analysis. Results: 90 medical records were analyzed, and the defining characteristics of the diagnoses were revealed by high blood pressure and the presence of proteinuria. The related factors were maternal age, weight gain, body mass index, history of hypertensive diseases, number of prenatal consultations and use of antihypertensive medication. Conclusion: the characteristics that more accurately predict the occurrence of the diagnosis investigated and the reduction of the severe forms of the disease were identified. KEYWORDS: Women's health; Pregnancy-induced hypertension; Health profile; Prenatal care. CARACTERÍSTICAS DEFINIDORAS Y FACTORES ASOCIADOS A LA OCURRENCIA DE LOS SÍNDROMES HIPERTENSIVOS GESTACIONALESRESUMEN: Objetivo: identificar las características definidoras y los factores relacionados en Síndromes Hipertensivos Gestacionales. Método: estudio longitudinal, retrospectivo, realizado en el centro de salud de prenatal de alto riesgo, en un municipio del oeste de Santa Catarina en 2016. Como criterios de inclusión se adoptaron: gestación única que no tenga resultado en aborto u óbito fetal, la fecha de la última menstruación entre enero y diciembre de 2015, y la presencia de diagnóstico del síndrome. Para el análisis de los...

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“…Meta-analysis of past studies enhances statistical power, which may highlight novel molecular pathways or strengthen the evidence for previously identified genes. Indeed, multiple meta-analyses have been performed for pre-eclampsia ( Kleinrouweler et al , 2013 ; Moslehi et al , 2013 ; Vaiman et al , 2013 ; van Uitert et al , 2015 ; Vaiman and Miralles, 2016 ; Brew et al , 2016 ) and preterm birth ( Eidem et al , 2015 ; Paquette et al , 2018 ), as well as for investigating sexual dimorphism of the placenta ( Buckberry et al , 2014 ) and understanding trophoblast differentiation in the context of hydatidiform moles ( Desterke et al , 2018 ). Nevertheless, lack of data access can hamper the ability to perform powerful meta-analyses.…”

Section: Knowledge Gaps and Future Directionsmentioning

confidence: 99%

Current approaches and developments in transcript profiling of the human placenta

Yong

Chan

2020

Human Reproduction Update

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BACKGROUND The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely discarded at delivery, providing a valuable resource to explore maternal-offspring health and disease in pregnancy. Genome-wide profiling of the human placental transcriptome provides an unbiased approach to study normal maternal–placental–foetal physiology and pathologies. OBJECTIVE AND RATIONALE To date, many studies have examined the human placental transcriptome, but often within a narrow focus. This review aims to provide a comprehensive overview of human placental transcriptome studies, encompassing those from the cellular to tissue levels and contextualize current findings from a broader perspective. We have consolidated studies into overarching themes, summarized key research findings and addressed important considerations in study design, as a means to promote wider data sharing and support larger meta-analysis of already available data and greater collaboration between researchers in order to fully capitalize on the potential of transcript profiling in future studies. SEARCH METHODS The PubMed database, National Center for Biotechnology Information and European Bioinformatics Institute dataset repositories were searched, to identify all relevant human studies using ‘placenta’, ‘decidua’, ‘trophoblast’, ‘transcriptome’, ‘microarray’ and ‘RNA sequencing’ as search terms until May 2019. Additional studies were found from bibliographies of identified studies. OUTCOMES The 179 identified studies were classifiable into four broad themes: healthy placental development, pregnancy complications, exposures during pregnancy and in vitro placental cultures. The median sample size was 13 (interquartile range 8–29). Transcriptome studies prior to 2015 were predominantly performed using microarrays, while RNA sequencing became the preferred choice in more recent studies. Development of fluidics technology, combined with RNA sequencing, has enabled transcript profiles to be generated of single cells throughout pregnancy, in contrast to previous studies relying on isolated cells. There are several key study aspects, such as sample selection criteria, sample processing and data analysis methods that may represent pitfalls and limitations, which need to be carefully considered as they influence interpretation of findings and conclusions. Furthermore, several areas of growing importance, such as maternal mental health and maternal obesity are understudied and the profiling of placentas from these conditions should be prioritized. WIDER IMPLICATIONS Integrative analysis of placental transcriptomics with other ‘omics’ (methylome, proteome and metabolome) and linkage with future outcomes from longitudinal studies is crucial in enhancing knowledge of healthy placental development and function, and in enabling the underlying causal mechanisms of pregnancy complications to be identified. Such understanding could help in predicting risk of future adversity and in designing interventions that can improve the health outcomes of both mothers and their offspring. Wider collaboration and sharing of placental transcriptome data, overcoming the challenges in obtaining sufficient numbers of quality samples with well-defined clinical characteristics, and dedication of resources to understudied areas of pregnancy will undoubtedly help drive the field forward.

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An Integrative Analysis of Preeclampsia Based on the Construction of an Extended Composite Network Featuring Protein-Protein Physical Interactions and Transcriptional Relationships

Cited by 16 publications

References 78 publications

Comparative transcriptomic analysis of human placentae at term and preterm delivery†

Comparative transcriptomic analysis of human placentae at term and preterm delivery†

Características Definidoras E Fatores Associados À Ocorrência Das Síndromes Hipertensivas Gestacionais*

Current approaches and developments in transcript profiling of the human placenta

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