Serum proteomics of mother-infant dyads carrying HLA-conferred type 1 diabetes risk
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Robert Moulder
PROVIDER: PXD047235 | panorama | Mon May 27 00:00:00 BST 2024
REPOSITORIES: PanoramaPublic
Similar Datasets
Project description:LC-MS/MS analysis formula was performed for sera from 22 mother-infant dyads with HLA-conferred susceptibility to type 1 diabetes that were weaned to either an extensively hydrolyzed or regular infant milk. The samples included three samples from each mother (at the beginning of third trimester, at the time of delivery and 3 months postpartum) and five samples from each child (cord blood, 3, 6, 9 and 12 months). Targeted proteomics was used to validate differences observed between the feeding groups.Correlations in protein intensities within the dyads were detected together with perinatal and age-related changes.
2024-05-27 | PXD046387 | Pride
Project description:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring.
Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants.
Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings.
Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.
| MSV000095983 | MassIVE
Project description:Human milk (breastmilk) is much more than nutrition for the infant, containing an array of regulatory agents with immunoprotective and developmental functions. Amongst those, microRNAs (miRNAs) have recently been identified, with their properties, roles, origin and distribution in breastmilk as well as in the mammary gland being still undetermined. In this study, we examined the miRNA profile of different fractions of human milk (cells and lipids) using the OpenArray system (Applied Biosystems, 770 miRNA species measured per sample) and compared it with maternal peripheral blood mononuclear cells (PBMCs) and plasma. Although PBMCs were the richest group in miRNA species, plasma showed very low expression pattern. Thus, the human milk fractions (cells, lipid) and skim milk (not being investigated in this study) were found to conserve higher levels of miRNAs than blood in general. Specifically, human milk cell miRNA quantity was found relatively close to PBMCs, and higher than milk lipids. Correlation and clustering analyses indicated that miRNA expression and types of milk cells were highly similar to those in lipids. Milk miRNAs showed a slight correlation to PBMCs, so PBMCs potentially are not contributing to milk miRNAs. Plasma was different to all other three groups in miRNA content and expression pattern. Further, two infant formulae (a plant-based and a cow milk-based) were compared to human milk and found to contain significantly fewer miRNA species than human milk cells and lipids (p>0.001). Taken together with previous studies on miRNAs, our findings demonstrate that human milk is one of the richest sources of miRNAs among human body fluids. As a non-invasive and plentiful source of miRNAs, human milk could be used as a disease biomarker for the mammary gland, with potential in assessing lactation performance. Finally, gene target and pathways analyses identified several target mRNAs regulated by miRNAs found to be abundant in breastmilk. Given the recently identified stability and function of food-derived miRNAs in regulating mammalian genes, we propose that breastmilk is a rich source of miRNA ingested by the infant during the first months of life, and which potentially contribute to early infant development. 10 exclusively breastfeeding dyads were recruited. 10 whole milk and 10 whole blood samples were collected and fractionated to obtain 10 milk cells, 10 milk lipid, 10 mononeucleoted blood cells (PBMCs), and 10 plasma. In addition to the above 40 samples, 2 infant formula were profiled. 4 different extraction kits were used, miRNeasy mini Kit for human milk cell and PBMC samples. miRCURY RNA Isolation-Biofluids Kit for human milk lipid samples and both infant formulae. mirVana PARIS Kit for plasma samples. NanoDrop 2000 and Bioanalyzer 2100 were used to determine concentration and purity of the extracted miRNA from all samples (n=42). miRNA OpenArray panel system (Life Technologies, CA, USA) was used to profile 754 human mature miRNAs in samples. RNU48, RNU44 and U6 rRNA were used as housekeeping controls for normalisation. ath-miR159a was used as a negative control for human samples. GeneGO and Ingenuity Pathway Analysis were used to determine biological pathways. Please note that normalization of miRNAs was done in R but without generating deltaCT values, thus [1] only the list of normalized miRNA with Ct vlaue between 8 and 29 and that detected in at least 4 samples out of 10 analysed in each group is provided ('normalized_miRNAs_list.txt') [2] the sample data tables contain raw data.
2015-03-30 | E-GEOD-66358 | biostudies-arrayexpress
Project description:Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from 8 women provided 5 paired-groups (cancer versus control) for analysis of differentially expressed proteins: 2 within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and 3 across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the 5 comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research.
2017-12-18 | PXD007066 | Pride
Project description:Complex oligosaccharides found in human milk play a vital role in gut microbiome development for the human infant. Bovine milk oligosaccharides (BMO) have similar structures with those derived from human milk, but have not been well studied for their effects on the healthy adult human gut microbiome. Healthy human subjects consumed BMO over two-week periods at two different doses and provided fecal samples. Metatranscriptomics of fecal samples was conducted to determine microbial and host gene expression in response to the supplement. Fecal samples were also analyzed by mass spectrometry to determine levels of undigested BMO. No changes were observed in microbiome activity across all participants. Repeated sampling enabled subject-specific analyses: four of six participants had minor, yet statistically significant, changes in microbial activity. No significant change was observed in the gene expression of host cells in stool. Levels of BMO excreted in feces after supplementation were not significantly different from placebo and were not correlated with dosage or expressed microbial enzyme levels. Collectively, these data suggest that BMO is fully digested in the human gastrointestinal tract prior to stool collection. Participants’ gut microbiomes remained stable but varied between individuals. Additionally, the unaltered host transcriptome provides further evidence for the safety of BMO as a dietary supplement or food ingredient.
2020-02-18 | GSE108809 | GEO
Project description:Bovine mastitis, the infection of the mammary gland which leads to great health and economic challenges for dairy farmers is accompanied by dramatic changes in the milk proteome. In this study of naturally occurring mastitis not only have the changes in the milk proteome been quantified in subclinical and clinical mastitis but simultaneous changes in the serum proteome have also been characterised and quantified. Milk and serum samples from healthy dairy cows (n=12) were compared to those of cows with subclinical (n=10) and clinical mastitis (n=112) using TMT label-based proteomic approach. The study included the milk and serum samples taken from thirty-two dairy cows ( kept on private farms located in Croatia. All cows were checked by physical examination. Somatic cells count (SCC) and mastitis test in milk samples were performed. According to the results, cows were assigned into three groups: Group I (control, n=10) consisted of healthy cows with SCC below 400,000 cells/ml on the monthly check-up and a negative mastitis test and without any clinical sign of mastitis. Group II (subclinical mastitis, n=12) comprised cows without clinical signs of mastitis but with SCC above 400,000 cells/ml on the monthly basis and a positive mastitis test at the time of sampling. Group III (clinical mastitis, n=10) consisted of cows with clinical signs of mastitis which include changes in milk appearance (flakes and clots in milk), different stages of udder inflammation (hyperemia, edema, pain, udder enlargement and elevated udder temperature) and disturbance of general health (depression, relaxed cold ears, dehydration, elevated body temperature, increased heart and respiratory rate, decreased ruminal contraction and decreased appetite). Blood samples were taken from v. coccygea and centrifuged at 3000 g for 15 min after clotting for two hours at room temperature. Serum samples were stored at -80°C until analysis. Milk samples were taken aseptically before the morning milking. First few streams were discarded. Teat ends were disinfected with cotton swabs soaked with 70% ethanol. Samples were taken into sterile tubes and transported to laboratory on ice within a few hours.
2021-05-26 | PXD022595 | Pride
Project description:It is unclear to what degree protein degradation occurs in the infant stomach and whether peptides previously annotated for bioactivity are released. This study combined nanospray liquid chromatography separation with time of flight mass spectrometry, comprehensive structural libraries and informatics to interrogate milk of three human mothers and the gastric aspirates from their 4–12 day post-partum infants. Milk from the mothers contained almost two hundred distinct peptides, demonstrating enzymatic degradation of milk proteins beginning either during lactation or between milk collection and feeding. In the gastric samples, 649 milk peptides were identified, demonstrating that digestion continues in the infant stomach. The majority of peptides in both the intact milk and gastric samples were derived from β-casein. The numbers of peptides from β-casein, lactoferrin, α-lactalbumin, lactadherin, κ-casein, serum albumin, bile-salt associated lipase and xanthine dehydrogenase/oxidase were significantly higher in the gastric samples than the milk samples (p<0.05). Six hundred three peptides were significantly different in abundance between milk and gastric samples (p<0.05). Most of the identified peptides have previously identified biological activity. Gastric proteolysis occurs in the term infant in the first two weeks of life releasing biologically active milk peptides with immunomodulatory, antibacterial, and calcium-binding activity of clinical relevance to the proximal intestinal tract.
2014-04-15 | PXD000688 | Pride
Project description:Biomarkers are needed to accurately predict and monitor type 1 diabetes progression during the substantially heterogeneous presymptomatic period of the disease development. To address this concern, we studied temporal changes in the plasma and serum proteomes of < 5-year-old children with HLA-conferred risk for type 1 diabetes by analysing longitudinal sample series that were collected at regular intervals between birth and diagnosis. Using mass spectrometry-based discovery proteomics, longitudinal plasma sample series from multiple autoantibody positive children who had rapidly progressed to type 1 diabetes before 4 years of age were analysed and compared with similar measurements from age and gender matched children who were either single autoantibody positive or autoantibody negative. Following analysis of the data with an additive Gaussian process regression model (LonGP), targeted proteomics was used to verify 11 biomarker candidates in a larger independent yet similar cohort of children with more frequent sampling points. The data reiterated extensive age related trends for protein levels in young children. Further, by combining the utility of LonGP together with the targeted analysis in an extended cohort, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes in comparison to autoantibody negative children.
2023-09-26 | PXD033744 | Pride
Project description:Severe eosinophilic asthma is characterized by chronic airway inflammation, oxidative stress and elevated proinflammatory cytokines, especially IL-5. Mepolizumab and benralizumab are both humanized IgG antibodies directed against IL-5 signaling, directly acting on eosinophils count. Together with the complexity of severe asthma classification and to the patient selection for the targeted treatment, there is also the urgency to clarify the follow-up of therapy to identify biomarkers, in addition to eosinophils, for the optimal duration of treatment, persistence of effectiveness and safety. To this purpose, here we performed a follow-up study by differential proteomic analysis on serum samples after 1 month and 6 months of both therapies and sera from healthy patients. Statistical analysis by PCA and heatmap analyses were performed, and identified proteins were used for enrichment analysis by MetaCore software. Analysis highlights 82 differences among all considered conditions. In particular, 30 referred to benralizumab time points (T0, T1B, T6B) and 24 to mepolizumab time points (T0, T1M, T6M) analyses. t-SNE and heatmap analyses evidences as the differential serum protein profile at 6 months of both treatments is more similar to that of the healthy subjects. Among the identified proteins, APOAI, APOC-II and APOC-III are up-regulated principally after six months of benralizumab treatment, plasminogen is up-regulated after six months of both treatments and ceruloplasmin, up-regulated already after 1 month of benralizumab, become higher after 6 months of mepolizumab. By enrichment analysis, identified proteins were related to lipid metabolism and transport, blood coagulation and ECM remodelling.
2022-04-01 | PXD029793 | Pride
Project description:Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes.
2008-06-11 | GSE11733 | GEO