Computational Tools for Proteomics

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

The Knepper Laboratory focuses on investigating the molecular mechanisms of water transport in the renal collecting duct and the pathophysiology of water balance disorders. Their research employs multi-omic methodologies, including protein mass spectrometry and various next-generation sequencing (NGS) techniques. A - Proteomics Tools: Mass spectrometers suitable for protein mass spectrometry have shown rapid advancements in performance capabilities, yielding extensive data for systems biology-oriented investigations. However, data processing tasks frequently pose limitations to progress in proteomics-based studies. To address this, the project is developing essential software tools for interpreting the substantial datasets acquired. Originally designed for internal use, these tools are also made available to other researchers at https://esbl.nhlbi.nih.gov/Bioinformatic%20Tools.htm. B - NGS Data Integration: An important objective of the laboratory is the identification of potential enhancers involved in the transcriptional regulation of genes such as Aqp2, which codes for a water channel crucial for kidney water transport. Achieving this entails integrating ATAC-seq data, histone H3K27 acetylation ChIP-seq data, and RNA-polymerase II ChIP-seq data. To accomplish precise enhancer identification through data integration, NGS-Integrator has been developed, leveraging Bayesian integration techniques. C - Big Data Integration of Multi-omic Data Sets: Addressing focused inquiries necessitates the integration of diverse -omic datasets. In response, the laboratory has developed Bayesian integration approaches. D - Antibody Design and Production: The demands of systems biology investigations often require the creation of new antibodies. Accordingly, software has been devised to predict optimal synthetic peptide sequences for antibody production. Details can be found at https://esbl.nhlbi.nih.gov/AbDesigner/. E - Software Dissemination: To facilitate software dissemination, algorithms are coded in Java or Python, ensuring platform independence and compatibility with various machines. Additionally, efforts are underway to offer online execution options wherever feasible. The software can be accessed at https://esbl.nhlbi.nih.gov/Bioinformatic%20Tools.htm. F - Data Resources: Gene Expression Atlases for Renal Epithelia: The intricate renal structure consists of numerous tubules, each comprising 14 sequential segments and at least 17 distinct cell types. Understanding kidney physiology and pathophysiology necessitates knowledge of gene expression in each cell type. The Epithelial Systems Biology Laboratory (ESBL) has harnessed RNA-seq, protein mass spectrometry, and single-cell RNA-seq to determine mRNA and protein abundances. The compiled data are shared with the global kidney research community through meticulously curated online databases, accessible via an index page at https://esbl.nhlbi.nih.gov/Databases/KSBP2/. G - Data Resources: Phosphoproteomics Databases: Regulation of renal transport, including collecting ducts, involves phosphorylation changes, often in response to vasopressin. The laboratory has amassed extensive phosphoproteomic data from renal tubule epithelia and disseminated it to researchers worldwide through carefully curated online databases. These databases are reachable through an index page at https://esbl.nhlbi.nih.gov/Databases/KSBP2/.