OmicNavigator: open-source software for the exploration, visualization, and archival of omic studies.

Background: The results of high-throughput biology ('omic') experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival.

A Methodological Assessment and Characterization of Genetically-Driven Variation in Three Human Phosphoproteomes.

Phosphorylation of proteins on serine, threonine, and tyrosine residues is a ubiquitous post-translational modification that plays a key part of essentially every cell signaling process. It is reasonable to assume that inter-individual variation in protein phosphorylation may underlie phenotypic differences, as has been observed for practically any other molecular regulatory phenotype. However, we do not know much about the extent of inter-individual variation in phosphorylation because it is quite challenging to perform a quantitative high throughput study to assess inter-individual variation in any post-translational modification.

High-Throughput Quantification of SH2 Domain-Phosphopeptide Interactions with Cellulose-Peptide Conjugate Microarrays.

The Src Homology 2 (SH2) domain family primarily recognizes phosphorylated tyrosine (pY) containing peptide motifs. The relative affinity preferences among competing SH2 domains for phosphopeptide ligands define "specificity space," and underpins many functional pY mediated interactions within signaling networks. The degree of promiscuity exhibited and the dynamic range of affinities supported by individual domains or phosphopeptides is best resolved by a carefully executed and controlled quantitative high-throughput experiment.

Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling.

Accurate annotation of protein coding regions is essential for understanding how genetic information is translated into function. We describe riboHMM, a new method that uses ribosome footprint data to accurately infer translated sequences. Applying riboHMM to human lymphoblastoid cell lines, we identified 7273 novel coding sequences, including 2442 translated upstream open reading frames.

The development and application of a quantitative peptide microarray based approach to protein interaction domain specificity space.

Protein interaction domain (PID) linear peptide motif interactions direct diverse cellular processes in a specific and coordinated fashion. PID specificity, or the interaction selectivity derived from affinity preferences between possible PID-peptide pairs is the basis of this ability. Here, we develop an integrated experimental and computational cellulose peptide conjugate microarray (CPCMA) based approach for the high throughput analysis of PID specificity that provides unprecedented quantitative resolution and reproducibility.

SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome.

Specific peptide ligand recognition by modular interaction domains is essential for the fidelity of information flow through the signal transduction networks that control cell behavior in response to extrinsic and intrinsic stimuli. Src homology 2 (SH2) domains recognize distinct phosphotyrosine peptide motifs, but the specific sites that are phosphorylated and the complement of available SH2 domains varies considerably in individual cell types. Such differences are the basis for a wide range of available protein interaction microstates from which signaling can evolve in highly divergent ways.

High-throughput analysis of peptide-binding modules.

Modular protein interaction domains (PIDs) that recognize linear peptide motifs are found in hundreds of proteins within the human genome. Some PIDs such as SH2, 14-3-3, Chromo, and Bromo domains serve to recognize posttranslational modification (PTM) of amino acids (such as phosphorylation, acetylation, methylation, etc.) and translate these into discrete cellular responses.

The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction.

Natural languages arise in an unpremeditated fashion resulting in words and syntax as individual units of information content that combine in a manner that is both complex and contextual, yet intuitive to a native reader. In an analogous manner, protein interaction domains such as the Src Homology 2 (SH2) domain recognize and "read" the information contained within their cognate peptide ligands to determine highly selective protein-protein interactions that underpin much of cellular signal transduction. Herein, we discuss how contextual sequence information, which combines the use of permissive and non-permissive residues within a parent motif, is a defining feature of selective interactions across SH2 domains.

The SH2 domain-containing proteins in 21 species establish the provenance and scope of phosphotyrosine signaling in eukaryotes.

The Src homology 2 (SH2) domains are participants in metazoan signal transduction, acting as primary mediators for regulated protein-protein interactions with tyrosine-phosphorylated substrates. Here, we describe the origin and evolution of SH2 domain proteins by means of sequence analysis from 21 eukaryotic organisms from the basal unicellular eukaryotes, where SH2 domains first appeared, through the multicellular animals and increasingly complex metazoans. On the basis of our results, SH2 domains and phosphotyrosine signaling emerged in the early Unikonta, and the numbers of SH2 domains expanded in the choanoflagellate and metazoan lineages with the development of tyrosine kinases, leading to rapid elaboration of phosphotyrosine signaling in early multicellular animals.

SH2 domains recognize contextual peptide sequence information to determine selectivity.

Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks.