Biology subjects

Morin, G. B.

Publications and source records attributed to Morin, G. B..

4 recordsLinked to original sources

bioRxiv2018

RawTools: Rapid and Dynamic Interrogation of Orbitrap Data Files for Mass Spectrometer System Management

Optimizing the quality of proteomics data collected from a mass spectrometer (MS) requires careful selection of acquisition parameters and proper assessment of instrument performance. Software tools capable of extracting a broad set of information from raw files, including meta, scan, quantification, and identification data are needed to provide guidance for MS system management. In this work, direct extraction and utilization of these data from Thermo Orbitrap raw files is demonstrated using the RawTools software. RawTools is a standalone tool for extracting meta and scan data directly from raw MS files generated on Thermo Orbitrap instruments. RawTools generates summarized and detailed plain text outputs after parsing individual raw files, including scan rates and durations, duty cycle characteristics, precursor and reporter ion quantification, and chromatography performance. RawTools also contains a diagnostic module that includes an optional preview database search for facilitating informed decision-making related to optimization of MS performance based on a variety of metrics. RawTools has been developed in C# and utilizes the Thermo RawFileReader library, and thus can process raw MS files with high speed and high efficiency on all major operating systems (Windows, MacOS, Linux). To demonstrate the utility of RawTools, extraction of meta and scan data from both individual and large collections of raw MS files was carried out to identify problematic characteristics of instrument performance. Taken together, the combined rich feature-set of RawTools with the capability for interrogation of MS and experiment performance makes this software a valuable tool for proteomics researchers.

bioinformatics↗

bioRxiv2018

YB-1 Is Critical For The Genesis And Progression Of KRAS Mutated Human Breast Cancer

Breast cancer heterogeneity has made it challenging to elucidate shared mechanisms that underpin properties that are critical to their growth in vivo. Here, we interrogate the role of YB-1 protein in the in vivo tumorigenic activity of de novo well as cell line models of human breast cancer. Short-hairpin RNA-mediated knockdown of YB-1 in MDA-MB-231 cells blocked both their local tumour-forming and lung-colonizing activity in transplanted immunodeficient mice. YB-1 knockdown also revealed its important role at early stages of human mammary cell transformation in the generation of invasive ductal carcinoma and ductal carcinoma in situ produced in mice transplanted with freshly isolated human mammary cells transduced, respectively, with KRASG12D, or myristoylated-AKT1. Conversely, upregulated expression of YB-1 in the poorly tumorigenic T47D cells enhanced this activity. Mechanistically, reducing YB-1 levels in MDA-MB-231 cells impaired their induction of HIF1, and G3BP1, known YB-1 translational targets and key elements of a stress-adaptive program.

cancer biology↗

bioRxiv2018

BAP1 Loss Predicts Therapeutic Vulnerability in Malignant Peritoneal Mesothelioma

BackgroundMalignant Peritoneal Mesothelioma (PeM) is a rare but frequently fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM yet exist. In the search for novel therapeutic target candidates in PeM, we performed a comprehensive integrative multi-omics analysis of 19 treatment-naive PeM tumors.\n\nResultsThe analysis identified PeM tumors with BAP1 loss to form a distinct molecular subtype characterized by distinct expression patterns of genes involved in chromatin remodeling, DNA repair pathway, and immune checkpoint receptor activation. This PeM subtype could potentially benefit from immune checkpoint, PARP, or HDAC inhibition therapies.\n\nConclusionsOur findings uncover BAP1 as a trackable prognostic and predictive biomarker, and refine PeM disease classification. This integrated molecular characterization provides a comprehensive foundation for developing PeM precision medicine.

cancer biology↗

bioRxiv2017

Genotoxin-induced transcriptional repression regulates selective protein aggregation

Upon genotoxic stress, dynamic relocalization events control DNA repair, and alterations of the transcriptome and proteome enabling stress recovery. How these events may influence one another is only partly known. Beginning with a cytological screen for genome maintenance proteins that move under stress, we find that, upon alkylation stress, the splicing factor Hsh155 localizes to both intranuclear and cytoplasmic protein quality control aggregates. Under stress, an ordered sequestration of Hsh155 occurs at nuclear and then cytoplasmic aggregates in a manner that is regulated by molecular chaperones. This dynamic behavior is preceded by a decrease in splicing efficiency. While DNA replication stress signaling is not required for Hsh155 sequestration, Hsh155 aggregation is cell cycle and TOR pathway dependent. Indeed, loss of a TORC1 regulated ribosomal protein gene transcription factor Sfp1 allows general aggregate formation but prevents Hsh155 recruitment. Together, our analyses suggest a model in which some proteins evicted from chromatin undergoing transcriptional remodeling during stress are targeted to protein quality control sites.

cell biology↗