Dataset Information

PROTEOMIC PROFILING OF AMNIOS FOR PRETERM BIRTH BIOMARKER DISCOVERY

ABSTRACT: Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. A consistent number of PTB are caused by microbial-induced preterm labor, mediated by an inflammatory process, that threatens both maternal and newborn health. In search for novel predictive biomarkers of PTB and PROM, and to improve understanding of infection related PTB, we performed a proteomic analysis of amnions from premature newborns. Samples were studied by Orbitrap mass spectrometry and bioinformatics analyses. A total of 6352 proteins were identified. A ranked core of 159 proteins maximized the discrimination between the different clinical stratification groups of amnions allowing to distinguish FIR 0 from FIR 3, stratified in function of MIR grade, among which Matrix metallopeptidase 9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential amnion-associated predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Placenta

SUBMITTER: Martina Bartolucci

LAB HEAD: Andrea Petretto

PROVIDER: PXD028343 | Pride | 2021-12-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Amnios.zip	Other
	HomoSapiens_UP000005640.fasta	Fasta
	Ramenghi_0417_Amnios_H112_16_077.raw	Raw
	Ramenghi_0417_Amnios_H146_16_A_103.raw	Raw
	Ramenghi_0417_Amnios_H146_16_B_115.raw	Raw

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Project description:Preterm birth (PTB) is defined as childbirth occurring at less than 37 completed weeks or 259 days of gestation. Premature babies have higher rates of cerebral palsy, sensory deficits, learning disabilities and respiratory illnesses that extend into adulthood. This lifelong morbidity results in high economic and social costs to families and communities. PTB is a syndrome initiated by multiple mechanisms, including infection or inflammation, uteroplacental ischaemia or haemorrhage, uterine overdistension, stress, and other immunologically mediated processes. Identifying and monitoring molecular signals in easily accessible body fluids that can diagnose or predict the risk of preterm labor in pregnant women will reduce or prevent PTBs. A number of studies reported the identification of putative biomarkers for PTB including protein, miRNA and hormone from different body fluids such as serum/plasma, cervical vaginal fluid, saliva and amniotic fluids. These putative biomarkers identified can largely be grouped into three main functional categories: inflammatory related molecules, placenta or fetal derived molecules and stress related molecules. In the past few years next generation sequencing (NGS) has become the major platform for miRNA analysis especially with body fluids. However, studies have shown significant sequence bias among different small RNA library preparation protocols. We have modified the small RNA library construction protocol which greatly reduces the sequence bias and increase miRNA coverage in sample. We also adapted a newly developed size exclusion chromatography (SEC) based EV purification protocol which can provide cleaner EVs compared to other methods. We are using these improved approaches to gain more reliable profile of circulating RNA in body fluid as well as its associated EVs. With these new approaches, we explore the possibility of using specific circulating miRNAs, specifically those encapsulated in EVs, as a noninvasive biomarker for PTB by comparing the miRNA profiles in maternal plasma, EV and EV-depleted plasma between individuals who had a spontaneous preterm birth and uncomplicated pregnancies.

Dataset Information

PROTEOMIC PROFILING OF AMNIOS FOR PRETERM BIRTH BIOMARKER DISCOVERY

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