NeuroLINCS Proteomics: Defining human-derived iPSC proteomes and protein signatures of pluripotency

NeuroLINCS 蛋白质组学:定义人类来源的 iPSC 蛋白质组和多能性蛋白质特征

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作者:Andrea D Matlock, Vineet Vaibhav, Ronald Holewinski, Vidya Venkatraman, Victoria Dardov, Danica-Mae Manalo, Brandon Shelley, Loren Ornelas, Maria Banuelos, Berhan Mandefro, Renan Escalante-Chong, Jonathan Li, Steve Finkbeiner, Ernest Fraenkel, Jeffrey Rothstein, Leslie Thompson, Dhruv Sareen, Clive

Abstract

The National Institute of Health (NIH) Library of integrated network-based cellular signatures (LINCS) program is premised on the generation of a publicly available data resource of cell-based biochemical responses or "signatures" to genetic or environmental perturbations. NeuroLINCS uses human inducible pluripotent stem cells (hiPSCs), derived from patients and healthy controls, and differentiated into motor neuron cell cultures. This multi-laboratory effort strives to establish i) robust multi-omic workflows for hiPSC and differentiated neuronal cultures, ii) public annotated data sets and iii) relevant and targetable biological pathways of spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Here, we focus on the proteomics and the quality of the developed workflow of hiPSC lines from 6 individuals, though epigenomics and transcriptomics data are also publicly available. Known and commonly used markers representing 73 proteins were reproducibly quantified with consistent expression levels across all hiPSC lines. Data quality assessments, data levels and metadata of all 6 genetically diverse human iPSCs analysed by DIA-MS are parsable and available as a high-quality resource to the public.

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