Complementarity of SOMAscan to LC-MS/MS and RNA-seq for quantitative profiling of human embryonic and mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSC) represent promising stem cell-derived therapeutics as indicated by their application in >500 clinical trials currently registered with the NIH. Tissue-derived MSC require invasive harvesting and imply donor-to-donor differences, to which embryonic stem cell (ESC)-derived MSC may provide an alternative and thus warrant thorough characterization. In continuation of our previous study where we compared in depth embryonic stem cells (ESC) and MSC from two sources (bone marrow and ESC-derived), we included the aptamer-based SOMAscan assay, complementing LC-MS/MS and RNA-seq data. Furthermore, SOMAscan, a targeted proteomics platform developed for analyzing clinical samples, has been benchmarked against established analytical platforms (LC-MS/MS and RNA-seq) using stem cell comparisons as a model.

A Systems-level Characterization of the Differentiation of Human Embryonic Stem Cells into Mesenchymal Stem Cells*[S]

“…The distribution for 6903 intersecting features is depicted in Fig. 5A with average correlation of 0.5 and a mode at 0.9 demonstrating better correlation than previously published for somatic cells (0.4) (49)or differentiating cells (0.2) (48), but in line with our previous study (50). PCA analysis was performed on differentially expressed features, which display good correlation (R Ͼ 0.7 and FDR Ͻ 0.05) (Fig.…”

Stability and reproducibility of proteomic profiles measured with an aptamer-based platform

“…Several previous studies have validated SOMAscan using other orthogonal proteomic platforms, including LC-MS/MS and ELISA 5 – 11 . In an analysis of human embryonic and mesenchymal stem cells, Billing and colleagues considered 408 proteins measured by SOMAscan, LC-MS/MS, and RNA sequencing and reported that 60% of the SOMAscan results were validated by the other two methods, which was comparable to results obtained when comparing LC-MS/MS and RNA sequencing to each other 5 .…”

“…Several previous studies have validated SOMAscan using other orthogonal proteomic platforms, including LC-MS/MS and ELISA 5 – 11 . In an analysis of human embryonic and mesenchymal stem cells, Billing and colleagues considered 408 proteins measured by SOMAscan, LC-MS/MS, and RNA sequencing and reported that 60% of the SOMAscan results were validated by the other two methods, which was comparable to results obtained when comparing LC-MS/MS and RNA sequencing to each other 5 . Murota and colleagues used SOMAscan to identify 33 biomarkers associated with rheumatoid arthritis and selected five proteins to validate the results using conventional immunoassays, including electrochemiluminescence assays, ELISA, and latex turbidimetric assays 6 .…”

“…SOMAscan allows measurement of proteins across a very broad dynamic range, from low abundant cytokines to albumin. SOMAscan has been validated in several studies which have compared proteomic measurements across different platforms 5 – 11 .…”

Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome

“…However, multiplex biological assays were recently combined with MS for the identification of molecules having a biological response and biomarkers of health relevance in an effect-directed approach. For example, gene reporter assays combined with LC-HRMS for determining bioactive estrogenic and anti-estrogenic compounds in environmental water samples (Jonker et al, 2015), cell-based reporter gene assays combined with LC-MS for studying metabolites of the human histamine H4 receptor ligands (Nijmeijer et al, 2012), and a multiplatform approach for protein biomarkers discovery using SOMAscan, a multiplexed aptamer-based technique, and LC-MS (Billing et al, 2016, McArdle et al, 2016). By looking at biological response molecules it can drive future studies on the biological systems affected by exposures (Rappaport, 2012) (Dennis et al, 2016a).…”