Project description:The worldwide increase in snack-food consumption associated with adoption of Westernized lifestyles provides an opportunity to introduce new nutritious foods into non-nutritious diets. We describe two 10-week-long pilot studies of obese or overweight individuals measured the effects of pea fiber- or orange fiber-containing snack food prototypes on the abundances of fecal microbiome glycoside hydrolases (GH) and polysaccharide lyases (PL), fecal glycan metabolism, and >1300 plasma proteins. Computational methods for feature selection plus contextual language processing software that extracts information from all PubMed abstracts referencing features of interest, identified treatment-discriminatory changes in GH and PL gene abundances that correlated with levels of fecal glycosidic linkages related to fiber metabolism, and plasma proteins representing diverse biological themes, including TGFβ/BMP-mediated fibrotic responses, VEGF-related angiogenic responses, P38/MAPK-associated immune cell biomarkers, and obesity-associated hormonal regulators. These results disclose fiber-snack prototype effects on microbiome function and host physiology in the context of varying background dietary practices.
Project description:This study used SomaScan v 4.1 to profile>7000 proteins in maternal plasma and asses changes with gestational age and maternal characteristics. The study proposed models to estimate the expected protein abundance so that future datasets can be normalized agains these expected value to obtain Multiples of the Mean values.
Project description:In order to investigate variations in the endotype of COVID19 patients, we completed an integrated analysis of 112 research participants, including 74 COVID19 patients versus 37 SARS-CoV-2 negative controls. COVID19 patients tested positive for SARS-CoV-2 infection by PCR and/or antibody testing and were hospitalized due to COVID19 symptoms, but none of them had developed severe pathology requiring ICU admission at the time of blood collection. The control group was recruited from the same hospital system but tested negative for SARS-CoV-2 infection. Research blood draws were obtained from consented participants and analyzed by matched SARS-CoV-2 seroconversion assays, plasma proteomics using two alternative platforms [mass-spectrometry (MS), and SOMAscan assays], 82-plex cytokine profiling using Meso Scale Discovery (MSD) assays, and immune cell profiling via mass cytometry (MC).
Project description:In this study, we evaluated the utility of proteomics to identify plasma proteins in healthy participants from a phase I clinical trial with IFNβ-1a and pegIFNβ-1a biologics to identify potential pharmacodynamic (PD) biomarkers. Using a linear mixed-effects model with repeated measurement for product-time interaction, we found that 248 and 528 analytes detected by the SOMAscan® assay were differentially expressed (p-value < 6.86E-06) between therapeutic doses of IFNβ-1a or pegIFNβ-1a, and placebo, respectively. We further prioritized signals based on peak change, area under the effect curve over the study duration, and overlap in signals from the two products. Analysis of prioritized datasets indicated activation of IFNB1 signaling and an IFNB signaling node with IL-6 as upstream regulators of the plasma protein patterns from both products. Increased TNF, IL-1B, IFNG, and IFNA signaling also occurred early in response to each product suggesting a direct link between each product and these upstream regulators. In summary, we identified longitudinal global PD changes in a large array of new and previously reported circulating proteins in healthy participants treated with IFNβ-1a and pegIFNβ-1a that may help identify novel single proteomic PD biomarkers and/or composite PD biomarker signatures as well as provide insight into the mechanism of action of these products. Independent replication is needed to confirm present proteomic results and to support further investigation of the identified candidate PD biomarkers for biosimilar product development.
Project description:This study used SomaScan v 4.1 to profile>7000 proteins in human plasma and assess changes with Sars-Cov-2 infection and with Covid-19 disease severity in pregnant and non-pregnant individuals.