Citations 2
ProtPipe: A Multifunctional Data Analysis Pipeline for Proteomics and Peptidomics
Li, Ziyi , Weller, Cory A. , Shah, Syed Islamuddin , Johnson, Nicholas L. , Hao, Ying , Roberts, Jessica P. , Guha, Deyaan, Bereda, Colleen , Klaisner, Sydney, Machado, Pedro , Zanovello, Matteo , Prudencio, Mercedes , Staff, Nathan P. , Fratta, Pietro , Petrucelli, Leonard , Cookson, Mark , Ward, Michael E. , Singleton, Andrew , Nalls, Mike A. , Fratta, Pietro , Shah, Syed I , Jarreau, Paige B , Roberts, Jessica , Guha, Deyaan , Bereda, Colleen , Klaisner, Sydney , Machado, Pedro M , Zanovello, Matteo , Prudencio, Mercedes , Oskarsson, Björn , Staff, Nathan P , Dickson, Dennis W , Fratta, Pietro , Petrucelli, Leonard , Narayan, Priyanka , Ward, Michael E , Singleton, Andrew B , Nalls, Mike A , Qi, Yue A , Li, Ziyi , Fratta, Pietro , Johnson, Nicholas L , Oskarsson, Björn , Dickson, Dennis W. , Qi, Yue
Genomics, Proteomics & Bioinformatics | November 22, 2024 | Volume: 22 | Issue: 6 | Pages: No page available
Abstract Mass spectrometry (MS) is a technique widely employed for the identification and characterization of proteins, with personalized medicine, systems biology, and biomedical applications. The application of MS-based proteomics advances our understanding of protein function, cellular signaling, and complex biological systems. MS data analysis is a critical process that includes identifying and quantifying proteins and peptides and then exploring their biological functions in downstream analyses. To address the complexities associated with MS data analysis, we developed ProtPipe to streamline and automate the processing and analysis of high-throughput proteomics and peptidomics datasets with DIA-NN preinstalled. The pipeline facilitates data quality control, sample filtering, and normalization, ensuring robust and reliable downstream analyses. ProtPipe provides downstream analyses, including protein and peptide differential abundance identification, pathway enrichment analysis, protein–protein interaction analysis, and major histocompatibility complex (MHC)–peptide binding affinity analysis. ProtPipe generates annotated tables and visualizations by performing statistical post-processing and calculating fold changes between predefined pairwise conditions in an experimental design. It is an open-source, well-documented tool available at https://github.com/NIH-CARD/ProtPipe, with a user-friendly web interface.
TMEM106B core deposition associates with TDP-43 pathology and is increased in risk SNP carriers for frontotemporal dementia
Marks, Jordan D. , Ayuso, Virginia Estades, Carlomagno, Yari , Yue, Mei, Todd, Tiffany W. , Hao, Ying , Li, Ziyi , McEachin, Zachary T. , Shantaraman, Anantharaman , Daughrity, Lillian M. , Jansen‐West, Karen , Calliari, Anna , Bejarano, Jesús González , DeTure, Michael , Rawlinson, Bailey, Castanedes‐Casey, Monica , Lilley, Meredith T. , Donahue, Megan , Jawahar, Vidhya Maheswari, Petersen, Ronald C. , Oskarsson, Björn , Graff‐Radford, Neill R. , Josephs, Keith A. , Seyfried, Nicholas T., Ward, Michael E. , Zhang, Yong‐Jie , Prudencio, Mercedes , Petrucelli, Leonard , Cook, Casey , Duong, Duc M , Daughrity, Lillian M , Jansen-West, Karen R , Shao, Wei , Calliari, Anna , Bejarano, Jesus Gonzalez , DeTure, Michael , Castanedes-Casey, Monica , Lilley, Meredith T , Donahue, Megan H , Boeve, Brad , Petersen, Ronald C , Knopman, David S. , Oskarsson, Björn , Wszolek, Z.K. , Dickson, Dennis W , Josephs, Keith A , Qi, Yue A , Seyfried, Nicholas T , Ward, Michael E , Zhang, Yong-Jie , Prudencio, Mercedes , Petrucelli, Leonard , Cook, Casey N , Li, Ziyi , Shantaraman, Anantharaman , Estades Ayuso, Virginia , Shao, Wei , Bharathi, Vidhya , Boeve, Bradley F. , Knopman, David S. , Wszołek, Zbigniew K. , Dickson, Dennis W. , Qi, Yue , Seyfried, Nicholas T.
Science Translational Medicine | January 17, 2024 | Volume: 16 | Issue: 730 | Pages: No page available
Genetic variation at the transmembrane protein 106B gene ( TMEM106B) has been linked to risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) through an unknown mechanism. We found that presence of the TMEM106B rs3173615 protective genotype was associated with longer survival after symptom onset in a postmortem FTLD-TDP cohort, suggesting a slower disease course. The seminal discovery that filaments derived from TMEM106B is a common feature in aging and, across a range of neurodegenerative disorders, suggests that genetic variants in TMEM106B could modulate disease risk and progression through modulating TMEM106B aggregation. To explore this possibility and assess the pathological relevance of TMEM106B accumulation, we generated a new antibody targeting the TMEM106B filament core sequence. Analysis of postmortem samples revealed that the TMEM106B rs3173615 risk allele was associated with higher TMEM106B core accumulation in patients with FTLD-TDP. In contrast, minimal TMEM106B core deposition was detected in carriers of the protective allele. Although the abundance of monomeric full-length TMEM106B was unchanged, carriers of the protective genotype exhibited an increase in dimeric full-length TMEM106B. Increased TMEM106B core deposition was also associated with enhanced TDP-43 dysfunction, and interactome data suggested a role for TMEM106B core filaments in impaired RNA transport, local translation, and endolysosomal function in FTLD-TDP. Overall, these findings suggest that prevention of TMEM106B core accumulation is central to the mechanism by which the TMEM106B protective haplotype reduces disease risk and slows progression.