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.
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:Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer’s disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here we investigate whether APOE allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes. Using the SOMAscan assay, we measured 1,305 plasma proteins from 53 homozygous, APOE3 and APOE4 subjects without dementia. We investigated the relationship of either the APOE-ε4 allele or amyloid positivity with plasma proteome changes by linear mixed effects modeling and ontology-based pathway and module trait correlation analyses. APOE4 is associated with plasma protein differences linked to atherosclerosis, tyrosine kinase activity, cholesterol transport, extracellular matrix, and synaptogenesis pathways. Independent of APOE4, we found that subjects likely harboring brain amyloid exhibit plasma proteome signatures associated with AD-linked pathways, including neurovascular dysfunction. Our results indicate that APOE4 status or presence of brain amyloid are associated with plasma proteomic shifts prior to the onset of symptoms, suggesting that systemic pathways in certain risk contexts may be plausible targets for disease modification.
Project description:We used SOMAscan to measure >1300 analytes in sera from healthy controls and patients with sJIA, MAS, sJIA-LD and other related diseases.
Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
Project description:Saliva based diagnostics is a rapidly evolving field due to the large potential of saliva and the simple sample collection. A systematic comparison of IgG antibody profiles in saliva and plasma is currently lacking in scientific literature. Our hypothesis is that IgG profiles are equal in blood and saliva. By showing the equality of the profiles and relative IgG antigenic reactivities towards proteins and peptides we provide evidence that plasma IgG reactivities can be inferred from saliva IgG reactivities. IgG antibodies were isolated from human saliva and plasma samples. The reactivities of IgG isolates were analysed on peptide microarrays displaying linear epitopes of EBV (EBNA1 protein) and HBV (Large envelope protein) virus. Peptide arrays were printed by JPT Peptide Technologies (Berlin, Germany). We show high similarity of saliva and plasma IgG profiles on these two platforms and argue for generalisation from this subset to the whole immunological IgG antibody profile.
Project description:Comparing between plasma cytokine proteins on AML patients with or without aGVHD Comparing between plasma cytokine proteins on AML patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation, Day+14
Project description:Purpose: There is a need for point-of-care diagnostics for future mass casualty events involving radiation exposure. The development of radiation exposure and dose prediction algorithms for biodosimetry is needed for screening of large populations during these scenarios, and exploration of the potential effects which sex, age, genetic heterogeneity, and physiological comorbidities may have on the utility of biodosimetry diagnostics is needed. In the current study, proteomic profiling was used to examine sex specific differences in age matched C57BL6 mice on the blood proteome following radiation exposure and the usefulness of development and application of biodosimetry algorithms using both male and female samples. Methods: C57BL6 male and female mice between 9-11 weeks of age received a single total body radiation exposure of either 2, 4 or 8 Gy with plasma collection at days 1, 3 and 7 post-irradiation. Plasma was then screened using the SomaScan v4.1 assay for ~7000 protein analytes. A subset panel of protein biomarkers demonstrated significant (FDR<0.05 and |logFC|>0.2) changes in expression following radiation exposure. All proteins were used for feature selection to build predictive models of radiation exposure using different sample and sex specific cohorts. Both binary (prediction of any radiation exposure) and multidose (prediction of specific radiation dose) model series were developed using either female and male samples combined or only female or only male samples. The binary series (Models 1, 2 and 3) and multidose series (Models 4, 5 and 6) series included female/male combined, female only and male only respectively. Results: Detectable values were obtained for all ~7000 proteins included in the SomaScan assay for all samples. Each model algorithm built using a unique sample cohort was validated with a training set of samples and tested with a separate new sample series. Overall predictive accuracies in the binary model series was ~100% at the model training level and when tested with fresh samples 97.9% for Model 1(Female and Male) and 100% for Model 2 (Female only) and Model 3 (Male only). When sex specific Models’ 2 and 3 were tested with the opposite sex, the overall predictive accuracy rate dropped to 62.5% for Model 2 and remained 100% for Model 3. The overall predictive accuracy rate in the multidose model series was 100% for all models at the model training level and when tested with fresh samples 83.3%, 75% and 83.3% for Multidose Models 4-6 respectively. When sex specific Models’ 5 (Female only) and Model 6 (Male only) were tested with the opposite sex the overall predictive accuracy rate dropped to 52.1% and 68.8% respectively. Conclusion: These models represent novel predictive panels of radiation responsive proteomic biomarkers and illustrate the utility and necessity of considering sex specific differences in development of radiation biodosimetry prediction algorithms. As sex specific differences were observed in this study, and as use of point-of-care radiation diagnostics in future mass casualty settings will necessarily include persons of both sexes, consideration of sex specific variation is essential to ensure these diagnostic tools have practical utility in the field.
Project description:Expression data from CD8+ T cells and CD68+ monocytes from patients with hemophagocytic lymphohistiocytosis, sepsis, and persistent systemic inflammatory response syndrome Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by pathologic immune activation in which prompt recognition and initiation of immune suppression is essential for survival. Children with HLH have many overlapping clinical features with critically ill children with sepsis and persistent systemic inflammatory response syndrome (SIRS) in whom alternative therapies are indicated. To determine if plasma biomarkers could differentiate HLH from other inflammatory conditions and to better define a ‘core inflammatory signature’ of HLH, concentrations of inflammatory plasma proteins were compared in 40 patients with HLH to 47 pediatric patients with severe sepsis or SIRS. Seventeen of 135 analytes were significantly different in HLH plasma compared to SIRS/sepsis, including increased interferon-gamma (IFNg)-regulated chemokines CXCL9, CXCL10 and CXCL11. Further, a 5-analyte plasma protein classifier including these chemokines was able to differentiate HLH from SIRS/sepsis. Gene expression in CD8+ T cells and CD68+ monocytes from blood were also enriched for IFNg pathway signatures in peripheral blood cells from patients with HLH compared to SIRS/sepsis. This study identifies differential expression of inflammatory proteins as a diagnostic strategy to identify critically ill children with HLH. Further, comprehensive unbiased analysis of inflammatory plasma proteins and global gene expression demonstrates that IFNg signaling is uniquely elevated in HLH. In addition to demonstrating the ability of diagnostic criteria for HLH, sepsis and SIRS to identify groups with distinct inflammatory patterns, results from this study support the potential for prospective evaluation of inflammatory biomarkers to aid in diagnosis of and optimizing therapeutic strategies for children with distinctive hyperinflammatory syndromes.