iDIA-QC: AI-empowered data-independent acquisition mass spectrometry-based quality control.

Quality control (QC) in mass spectrometry (MS)-based proteomics is mainly based on data-dependent acquisition (DDA) analysis of standard samples. Here, we collect 2754 files acquired by data independent acquisition (DIA) and paired 2638 DDA files from mouse liver digests using 21 mass spectrometers across nine laboratories over 31 months. Our data demonstrate that DIA-based LC-MS/MS-related consensus QC metrics exhibit higher sensitivity compared to DDA-based QC metrics in detecting changes in LC-MS status.

WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death.

Mutations in the macroautophagy/autophagy gene cause β-propeller protein-associated neurodegeneration (BPAN); however the molecular and cellular mechanism of the disease process is largely unknown. Here we generated constitutive knockout (KO) mice that displayed cognitive impairments, abnormal synaptic transmission and lesions in several brain regions. Immunohistochemistry analysis showed loss of neurons in prefrontal cortex and basal ganglion in aged mice, and increased apoptosis in prefrontal cortex, recapitulating a hallmark of neurodegeneration.

Analysis of neuronal phosphoproteome reveals PINK1 regulation of BAD function and cell death.

PINK1 mutations that disrupt its kinase activity cause autosomal recessive early onset Parkinson's disease (PD). Although research in recent years has elucidated a PINK1-Parkin pathway of mitophagy activation that requires PINK1 kinase activity, mitophagy-independent functions of PINK1 and their possible roles in PD pathogenesis have been proposed. Using an unbiased quantitative mass spectrometry approach to analyze the phosphoproteome in primary neurons from wild type and Pink1 knockout mice after mitochondrial depolarization, we uncovered PINK1-regulated phosphorylation sites, which involve coordinated activation of multiple signaling pathways that control cellular response to stress.

Large-Scale Identification of Protein Crotonylation Reveals Its Role in Multiple Cellular Functions.

Lysine crotonylation on histones is a recently identified post-translational modification that has been demonstrated to associate with active promoters and to directly stimulate transcription. Given that crotonyl-CoA is essential for the acyl transfer reaction and it is a metabolic intermediate widely localized within the cell, we postulate that lysine crotonylation on nonhistone proteins could also widely exist. Using specific antibody enrichment followed by high-resolution mass spectrometry analysis, we identified hundreds of crotonylated proteins and lysine residues.