Aafaque Ahmad Khan

Bio: Aafaque Ahmad Khan is an academic researcher from KIIT University. The author has contributed to research in topics: Signal transduction & Proteomics. The author has an hindex of 14, co-authored 25 publications receiving 2415 citations.

A draft map of the human proteome

Abstract: The availability of human genome sequence has transformed biomedical research over the past decade. However, an equivalent map for the human proteome with direct measurements of proteins and peptides does not exist yet. Here we present a draft map of the human proteome using high-resolution Fourier-transform mass spectrometry. In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins encoded by 17,294 genes accounting for approximately 84% of the total annotated protein-coding genes in humans. A unique and comprehensive strategy for proteogenomic analysis enabled us to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-coding RNAs and upstream open reading frames. This large human proteome catalogue (available as an interactive web-based resource at http://www.humanproteomemap.org) will complement available human genome and transcriptome data to accelerate biomedical research in health and disease.

Plasma Proteome Database as a resource for proteomics research: 2014 update

Abstract: Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of Human Proteome Organization's (HUPO's) pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10,546 proteins detected in serum/plasma of which 3784 have been reported in two or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their data set. We believe that PPD will facilitate both clinical and basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts.

A pathway map of glutamate metabolism

Abstract: Glutamate metabolism plays a vital role in biosynthesis of nucleic acids and proteins. It is also associated with a number of different stress responses. Deficiency of enzymes involved in glutamate metabolism is associated with various disorders including gyrate atrophy, hyperammonemia, hemolytic anemia, γ-hydoxybutyric aciduria and 5-oxoprolinuria. Here, we present a pathway map of glutamate metabolism representing metabolic intermediates in the pathway, 107 regulator molecules, 9 interactors and 3 types of post-translational modifications. This pathway map provides detailed information about enzyme regulation, protein-enzyme interactions, post-translational modifications of enzymes and disorders due to enzyme deficiency. The information included in the map was based on published experimental evidence reported from mammalian systems.

A network map of Interleukin-10 signaling pathway.

Abstract: Interleukin-10 (IL-10) is an anti-inflammatory cytokine with important immunoregulatory functions It is primarily secreted by antigen-presenting cells such as activated T-cells, monocytes, B-cells and macrophages In biologically functional form, it exists as a homodimer that binds to tetrameric heterodimer IL-10 receptor and induces downstream signaling IL-10 is associated with survival, proliferation and anti-apoptotic activities of various cancers such as Burkitt lymphoma, non-Hodgkins lymphoma and non-small scell lung cancer In addition, it plays a central role in survival and persistence of intracellular pathogens such as Leishmania donovani, Mycobacterium tuberculosis and Trypanosoma cruzi inside the host The signaling mechanisms of IL-10 cytokine are not well explored and a well annotated pathway map has been lacking To this end, we developed a pathway resource by manually annotating the IL-10 induced signaling molecules derived from literature The reactions were categorized under molecular associations, activation/inhibition, catalysis, transport and gene regulation In all, 37 molecules and 76 reactions were annotated The IL-10 signaling pathway can be freely accessed through NetPath, a resource of signal transduction pathways previously developed by our group

A multicellular signal transduction network of AGE/RAGE signaling.

Abstract: Advanced glycation end products (AGEs) are heterogeneous glycated products of proteins, lipids and nucleotides. The major receptor for AGEs, known as receptor for advanced glycation end products (RAGE or AGER), is a multi-ligand transmembrane receptor of immunoglobulin superfamily. It has an extracellular region, a transmembrane domain and a short cytoplasmic domain. Extracellular region of RAGE consists of one V type (critical for ligand binding) and two C type immunoglobulin domains (Schmidt et al. 1994a, b). Although the short cytoplasmic tail of 43 amino acid residues is found to be important for the signaling events mediated by RAGE, it does not have any known domain or motif (Neeper et al. 1992). The other cell surface receptors for AGEs include dolichyl-diphosphooligosaccharide-protein glycosyltransferase (AGE-R1) (Li et al. 1996), protein kinase C substrate, 80KH phosphoprotein (AGE-R2) (Goh et al. 1996), galectin-3 (AGE-R3) (Vlassara et al. 1995), and class A macrophage scavenger receptors type I and II. RAGE is also considered as a pattern recognition receptor due to its ability to bind different AGEs. RAGE has numerous extracellular ligands in addition to AGEs, which include extracellular high mobility group box-1 (HMGB1), S100 family of calcium binding proteins and amyloid-beta peptide (Fritz 2011). RAGE is expressed in diverse tissues such as lung, heart, kidney, brain, and skeletal muscle and in a variety of cells including endothelial cells, macrophages/monocytes, neutrophils, and lymphocytes (Brett et al. 1993; Ding and Keller 2005; Neeper et al. 1992). RAGE has been implicated in the pathogenesis of diverse diseases such as diabetes, cardiovascular disorders, arthritis, cancers and neurological disorders (Yan et al. 2009). Interactions of AGEs with their receptors alter cell function through the generation of free radicals (Schmidt et al. 1994a, b). In diabetes, interaction of AGEs with RAGE induces oxidative stress and inflammatory reactions thereby resulting in vascular damage and related complications (Yamagishi 2011). RAGE also plays an important role in the progression of atherosclerosis through oxidative stress and proinflammatory responses (Sun et al. 2009). Expression of RAGE in synovial tissue, T cells, B cells and macrophages of arthritic patients implies its significance in inflammatory joint disorders (Drinda et al. 2005). Overexpression of RAGE has also been reported in various types of cancers such as pancreatic, gastric, breast, lung cancers and lymphoma (Logsdon et al. 2007). Knockdown of RAGE expression was shown to inhibit ductal neoplasia in an animal model of pancreatic cancer (DiNorcia et al. 2012). A recent study by Liang et al. reported that the inactivation of RAGE in colorectal cancer cells reduced angiogenesis (Liang et al. 2011). The signaling events mediated by RAGE are complex due to the diversity of its ligands and their diverse effects mediated in different cell types. AGE/RAGE signaling in endothelial cells is reported to modulate oxidative stress, inflammation, apoptosis, autophagy, endothelial-mesenchymal-transition, endothelial permeability and dysfunction (Toma et al. 2009; Xu et al. 2010; Li et al. 2011; Xie et al. 2011; Ma et al. 2010; Del Turco et al. 2011). In smooth muscle cells, AGE/RAGE interaction leads to generation of reactive oxygen species, autophagy, proliferation and calcification (Yoon et al. 2009; Hu et al. 2012; Yuan et al. 2011; Tanikawa et al. 2009). AGE/RAGE signaling is reported to mediate proliferation in lymphocytes (Takahashi et al. 2010). In fibroblasts, it induces migration, inflammation and apoptosis (Liu et al. 2010; Shimoda et al. 2011). A diverse array of molecules and signaling modules were identified to be activated by RAGE depending on the intensity and duration of RAGE ligation. Specific signaling modules such as ERK1/2 (Lander et al. 1997), p38 MAPK (Lander et al. 1997), CDC42/RAC (Bondeva et al. 2011), SAPK/JNK (Hu et al. 2012) and NF-κB (Liu et al. 2010) have been shown to be triggered by AGE/RAGE interaction in different cell types. Currently, there are no resources, which contain RAGE signaling pathway data for visualization and analysis. Therefore, we have gathered signaling pathway reactions induced by AGE/RAGE interaction in diverse cell types and tissues from literature. We have also cataloged genes transcriptionally regulated by AGE/RAGE system in humans along with their transcriptional regulators. We have provided the AGE/RAGE signaling pathway data to scientific community through NetPath (http://www.netpath.org), a resource of signaling pathways developed by us (Kandasamy et al. 2010).

Tissue-based map of the human proteome

Abstract: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Enrichr: a comprehensive gene set enrichment analysis web server 2016 update

Abstract: Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present a significant update to one of the tools in this domain called Enrichr. Enrichr currently contains a large collection of diverse gene set libraries available for analysis and download. In total, Enrichr currently contains 180 184 annotated gene sets from 102 gene set libraries. New features have been added to Enrichr including the ability to submit fuzzy sets, upload BED files, improved application programming interface and visualization of the results as clustergrams. Overall, Enrichr is a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries. Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.

2016 update of the PRIDE database and its related tools

Abstract: The PRoteomics IDEntifications (PRIDE) database is one of the world-leading data repositories of mass spectrometry (MS)-based proteomics data Since the beginning of 2014, PRIDE Archive (http://wwwebiacuk/pride/archive/) is the new PRIDE archival system, replacing the original PRIDE database Here we summarize the developments in PRIDE resources and related tools since the previous update manuscript in the Database Issue in 2013 PRIDE Archive constitutes a complete redevelopment of the original PRIDE, comprising a new storage backend, data submission system and web interface, among other components PRIDE Archive supports the most-widely used PSI (Proteomics Standards Initiative) data standard formats (mzML and mzIdentML) and implements the data requirements and guidelines of the ProteomeXchange Consortium The wide adoption of ProteomeXchange within the community has triggered an unprecedented increase in the number of submitted data sets (around 150 data sets per month) We outline some statistics on the current PRIDE Archive data contents We also report on the status of the PRIDE related stand-alone tools: PRIDE Inspector, PRIDE Converter 2 and the ProteomeXchange submission tool Finally, we will give a brief update on the resources under development 'PRIDE Cluster' and 'PRIDE Proteomes', which provide a complementary view and quality-scored information of the peptide and protein identification data available in PRIDE Archive

The landscape of long noncoding RNAs in the human transcriptome

Abstract: Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. We applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes. Over 68% (58,648) of genes were classified as lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific, disease-associated lncRNA expression, we employed non-parametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. The lncRNA landscape characterized here may shed light on normal biology and cancer pathogenesis and may be valuable for future biomarker development.

Endogenous microRNA sponges: evidence and controversy.

Abstract: The competitive endogenous RNA (ceRNA) hypothesis proposes that transcripts with shared microRNA (miRNA) binding sites compete for post-transcriptional control. This hypothesis has gained substantial attention as a unifying function for long non-coding RNAs, pseudogene transcripts and circular RNAs, as well as an alternative function for messenger RNAs. Empirical evidence supporting the hypothesis is accumulating but not without attracting scepticism. Recent studies that model transcriptome-wide binding-site abundance suggest that physiological changes in expression of most individual transcripts will not compromise miRNA activity. In this Review, we critically evaluate the evidence for and against the ceRNA hypothesis to assess the impact of endogenous miRNA-sponge interactions.