Omics
Functional Characterization and Comparison of Plasmodium falciparum Proteins as Targets of Transmission-blocking AntibodiesThe malaria agent Plasmodium falciparum continues to evade control efforts. Despite multiple datasets for the Plasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development. We demonstrate the use of rational screens and comparative functional assessments in identifying proteins of the P. falciparum transmission pathway and establishing a robust pre-clinical TBV pipeline.
Citrullinome of Porphyromonas gingivalis Outer Membrane Vesicles: Confident Identification of Citrullinated PeptidesThe citrullinome of P. gingivalis outer membrane vesicles (OMV) has been explored by a novel two-dimensional separation system combined with high resolution mass spectrometry and in-house build software. Analysis of OMVs from wild-type and two PPAD mutants resulted in confident discrimination based on citrullinated peptides. In the wild-type citrullinome 78 proteins were identified having a total of 161 validated citrullination sites. A single citrullination was identified in the C351A mutant and none in the ΔPPAD mutant.
Targeted and Interactome Proteomics Revealed the Role of PHD2 in Regulating BRD4 Proline HydroxylationTargeted quantification assays using MS-based parallel-reaction monitoring and biochemical analysis revealed PHD2 as a key regulatory enzyme of BRD4 proline hydroxylation. Quantitative MS-based interactome and biochemical analyses revealed the functional significance of the proline hydroxylation modification pathway in BRD4-mediated protein-protein interactions and transcriptional activation. Taken together, these results provided mechanistic insights into the oxygen-dependent modification of BRD4 and revealed new roles of the proline hydroxylation pathway in regulating BRD4-mediated protein-protein interaction and gene expression.
Associations of the Fecal Microbial Proteome Composition and Proneness to Diet-induced ObesityIndividuals exhibit marked heterogeneity in the degree of adiposity that results from consumption of an obesogenic diet. We hypothesized that markers of inflammation, fecal microbiome, and/or proteome composition might associate with heterogeneity in diet-induced obesity. We found the fecal proteome, which was comprised of microbial proteins that changed markedly upon exposure to the obesogenic diet associated with extent of obesity and associated dysglycemia. These results suggest the fecal microbial proteome plays a role in diet-induced obesity.
Graph Algorithms for Condensing and Consolidating Gene Set Analysis ResultsWeighted set cover and affinity propagation algorithms are used to combine results from multiple enrichment analyses. Weighted set cover first condenses enriched gene sets to use the fewest number of gene sets that cover all relevant genes. Affinity propagation then clusters the enriched pathways and selects the most representative set. Together they facilitate interpretation of multiple enrichment analysis results. A demonstration of its utility highlights both general and unique pathways associated with cancer survival across seven cancer types.
Correlation Analysis of Histopathology and Proteogenomics Data for Breast CancerHistopathology images are important for cancer diagnosis and prognosis. We extracted quantitative morphological features from breast cancers images and systematically analyzed their relationships with proteins and mRNAs. We observed concordant correlation patterns between image-protein and image-RNA and identified four cancer-related biological processes associated with morphological features related to different tumor components. Further, we observed that proteomic data reveal unique protein-related biological processes associated with morphology. Finally, prognostic morphological features were identified, and their roles are consistent with the underlying biological processes.
Hdac4 Interactions in Huntington's Disease Viewed Through the Prism of MultiomicsThe histone deacetylase Hdac4 is known to contribute to the progression of Huntington's Disease (HD), but the underlying mechanisms remain unknown. Here, we defined the endogenous interactome of Hdac4 in the brain of HD mouse models, characterizing their polyQ- and age-dependence in affected tissues. Further integration with proteome and transcriptome data sets reveals the disease-induced enhancement of Hdac4 interactions with vesicular sorting proteins, including the WASH complex. This may contribute to the known decreased synaptic functions in Huntington's Disease.
Simultaneous Improvement in the Precision, Accuracy, and Robustness of Label-free Proteome Quantification by Optimizing Data Manipulation ChainsHigh-quality label-free proteome quantification (LFQ) is valuable for clinical and pharmaceutical studies yet remains extremely challenging despite technical advances. Particularly, fluctuating precision, limited robustness, and compromised accuracy are known issues. Here, we described and validated a new strategy enabling the discovery of the LFQs of simultaneously enhanced precision, robustness, and accuracy from thousands of LFQ manipulation chains. In the proof-of-concept study, this strategy showed superior ability in identifying well-performing LFQs. An online tool incorporating this novel strategy was also developed.