The implications of APOBEC3-mediated C-to-U RNA editing for human disease.

Intra-organism biodiversity is thought to arise from epigenetic modification of constituent genes and post-translational modifications of translated proteins. Here, we show that post-transcriptional modifications, like RNA editing, may also contribute. RNA editing enzymes APOBEC3A and APOBEC3G catalyze the deamination of cytosine to uracil.

The Role of C-to-U RNA Editing in Human Biodiversity.

Intra-organism biodiversity is thought to arise from epigenetic modification of our constituent genes and post-translational modifications after mRNA is translated into proteins. We have found that post-transcriptional modification, also known as RNA editing, is also responsible for a significant amount of our biodiversity, substantively expanding this story. The APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family RNA editing enzymes APOBEC3A and APOBEC3G catalyze the deamination of cytosines to uracils (C>U) in specific stem-loop structures.

Integrating Multi-Omics Data to Construct Reliable Interconnected Models of Signaling, Gene Regulatory, and Metabolic Pathways.

Alteration of the status of the metabolic enzymes could be a probable way to regulate metabolic reprogramming, which is a critical cellular adaptation mechanism especially for cancer cells. Coordination among biological pathways, such as gene-regulatory, signaling, and metabolic pathways is crucial for regulating metabolic adaptation. Also, incorporation of resident microbial metabolic potential in human body can influence the interplay between the microbiome and the systemic or tissue metabolic environments.

Association of C>U RNA Editing with Human Disease Variants.

RNA-editing is an important post-transcriptional RNA sequence modification performed by two catalytic enzymes, "ADAR"(A>I) and "APOBEC"(C>U). Although APOBEC-mediated C>U editing has been associated with a number of human cancers, the extent of C>U editing in human disease remains unclear. Here, we performed an association study and found that at least 1293 human disease variants occur at sites predicted by sequence motif analysis (RNASee protocol) to undergo APOBEC3A/G C>U editing.

Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma.

As malignant transformation requires synchronization of growth-driving signaling (S) and metabolic (M) pathways, defining cancer-specific S-M interconnected networks (SMINs) could lead to better understanding of oncogenic processes. In a systems-biology approach, we developed a mathematical model for SMINs in mutated EGF receptor (EGFRvIII) compared to wild-type EGF receptor (EGFRwt) expressing glioblastoma multiforme (GBM). Starting with experimentally validated human protein-protein interactome data for S-M pathways, and incorporating proteomic data for EGFRvIII and EGFRwt GBM cells and patient transcriptomic data, we designed a dynamic model for EGFR-driven GBM-specific information flow.

Protein sites with more coevolutionary connections tend to evolve slower, while more variable protein families acquire higher coevolutionary connections.

: Amino acid exchanges within proteins sometimes compensate for one another and could therefore be co-evolved. It is essential to investigate the intricate relationship between the extent of coevolution and the evolutionary variability exerted at individual protein sites, as well as the whole protein. : In this study, we have used a reliable set of coevolutionary connections (sites within 10Å spatial distance) and investigated their correlation with the evolutionary diversity within the respective protein sites.

Integrative genomic and network analysis identified novel genes associated with the development of advanced cervical squamous cell carcinoma.

Background: CSCC is one of the most common cancer affecting women globally. Though it is caused by the infection of hrHPV but long latency period for malignant outcome in only a subset of hrHPV infected women indicates involvement of additional alterations, primarily CNVs. Here, we showed how CNVs played a crucial role in development of advanced tumors (stage III/IV) in Indian patients.

Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy.

Background: Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule.

MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features.

Oral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised.

PALM-IST: Pathway Assembly from Literature Mining--an Information Search Tool.

Manual curation of biomedical literature has become extremely tedious process due to its exponential growth in recent years. To extract meaningful information from such large and unstructured text, newer and more efficient mining tool is required. Here, we introduce PALM-IST, a computational platform that not only allows users to explore biomedical abstracts using keyword based text mining but also extracts biological entity (e.

SPEER-SERVER: a web server for prediction of protein specificity determining sites.

Sites that show specific conservation patterns within subsets of proteins in a protein family are likely to be involved in the development of functional specificity. These sites, generally termed specificity determining sites (SDS), might play a crucial role in binding to a specific substrate or proteins. Identification of SDS through experimental techniques is a slow, difficult and tedious job.