Abstract

Network theory is now a method of choice to gain insights in understanding protein structure, folding and function. In combination with molecular dynamics (MD) simulations, it is an invaluable tool with widespread applications such as analyzing subtle conformational changes and flexibility regions in proteins, dynamic correlation analysis across distant regions for allosteric communications, in drug design to reveal alternative binding pockets for drugs, etc. Updated version of NAPS now facilitates network analysis of the complete repertoire of these biomolecules, i.e., proteins, protein–protein/nucleic acid complexes, MD trajectories, and RNA. Various options provided for analysis of MD trajectories include individual network construction and analysis of intermediate time-steps, comparative analysis of these networks, construction and analysis of average network of the ensemble of trajectories and dynamic cross-correlations. For protein–nucleic acid complexes, networks of the whole complex as well as that of the interface can be constructed and analyzed. For analysis of proteins, protein–protein complexes and MD trajectories, network construction based on inter-residue interaction energies with realistic edge-weights obtained from standard force fields is provided to capture the atomistic details. Updated version of NAPS also provides improved visualization features, interactive plots and bulk execution. URL: http://bioinf.iiit.ac.in/NAPS/

Abstract

Diffuse Large B-cell Lymphoma (DLBCL) is a highly heterogeneous cancer of B cells. Apart from cell-of-origin, genetic variations have been observed to contribute towards heterogeneity leading to different pathogenic mechanisms and overall survival outcomes. Various classification schemes have been proposed that may aid in risk stratification and developing new therapeutics for those who fail frontline therapy. This mini review highlights the significance of genetic variations as biomarkers for DLBCL and ease in extending it to clinical setting.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the aggressive form of haematological malignancies with relapse/refractory in ~ 40% of cases. It mostly develops due to accumulation of various genetic and epigenetic variations that contribute to its aggressiveness. Though large-scale structural alterations have been reported in DLBCL, their functional role in pathogenesis and as potential targets for therapy is not yet well understood. In this study we performed detection and analysis of copy number variations (CNVs) in 11 human DLBCL cell lines (4 activated B-cell–like [ABC] and 7 germinal-centre B-cell–like [GCB]), that serve as model systems for DLBCL cancer cell biology. Significant heterogeneity observed in CNV profiles of these cell lines and poor prognosis associated with ABC subtype indicates the importance of individualized screening for diagnostic and prognostic targets. Functional analysis of key cancer genes exhibiting copy alterations across the cell lines revealed activation/disruption of ten potentially targetable immuno-oncogenic pathways. Genome guided in silico therapy that putatively target these pathways is elucidated. Based on our analysis, five CNV-genes associated with worst survival prognosis are proposed as potential prognostic markers of DLBCL.

Abstract

Discovery of copy number variations (CNVs), a major category of structural variations, have dramatically changed our understanding of differences between individuals and provide an alternate paradigm for the genetic basis of human diseases. CNVs include both copy gain and copy loss events and their detection genome-wide is now possible using high-throughput, low-cost next generation sequencing (NGS) methods. However, accurate detection of CNVs from NGS data is not straightforward due to non-uniform coverage of reads resulting from various systemic biases. We have developed an integrated platform, iCopyDAV, to handle some of these issues in CNV detection in whole genome NGS data. It has a modular framework comprising five major modules: data pre-treatment, segmentation, variant calling, annotation and visualization. An important feature of iCopyDAV is the functional annotation module that enables the user to identify and prioritize CNVs encompassing various functional elements, genomic features and disease-associations. Parallelization of the segmentation algorithms makes the iCopyDAV platform even accessible on a desktop. Here we show the effect of sequencing coverage, read length, bin size, data pre-treatment and segmentation approaches on accurate detection of the complete spectrum of CNVs. Performance of iCopyDAV is evaluated on both simulated data and real data for different sequencing depths. It is an open-source integrated pipeline available at https://github.com/vogetihrsh/icopydav and as Docker’s image at http://bioinf.iiit.ac.in/icopydav/.

Abstract

Discovery of copy number variations (CNVs), a major category of structural variations, have dramatically changed our understanding of differences between individuals and provide an alternate paradigm for the genetic basis of human diseases. CNVs include both copy gain and copy loss events and their detection genome-wide is now possible using high-throughput, low-cost next generation sequencing (NGS) methods. However, accurate detection of CNVs from NGS data is not straightforward due to non-uniform coverage of reads resulting from various systemic biases. We have developed an integrated platform, iCopyDAV, to handle some of these issues in CNV detection in whole genome NGS data. It has a modular framework comprising five major modules: data pre-treatment, segmentation, variant calling, annotation and visualization. An important feature of iCopyDAV is the functional annotation module that enables the user to identify and prioritize CNVs encompassing various functional elements, genomic features and disease-associations. Parallelization of the segmentation algorithms makes the iCopyDAV platform even accessible on a desktop. Here we show the effect of sequencing coverage, read length, bin size, data pre-treatment and segmentation approaches on accurate detection of the complete spectrum of CNVs. Performance of iCopyDAV is evaluated on both simulated data and real data for different sequencing depths. It is an open-source integrated pipeline available at https://github.com/vogetihrsh/icopydav and as Docker’s image at http://bioinf.iiit.ac.in/icopydav/.

Abstract

In the last decade, discovery of copy number variations (CNVs) have dramatically changed our understanding of differences between individuals. CNVs include both additional copies of sequence (duplications) and loss of genetic material (deletions) and provide an alternate paradigm for the genetic basis of human diseases. Genome-wide CNV detection is now possible using high-throughput, low-cost next generation sequencing (NGS) methods. Nature of NGS data demands various preprocessing and pretreatment steps before extracting any meaningful information. Among the plethora of variant calling methods available, R-based methods offer flexible environment, facilitating choice of various methods depending on the type of data or type of analysis to be performed. Here we give a pipeline for various steps involved in CNV detection in NGS data using R-based algorithms and packages.

Abstract

Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue–residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the

Abstract

Drought is one of the major environmental stress conditions affecting the yield of rice across the globe. Unraveling the functional roles of the drought-responsive genes and their underlying molecular mechanisms will provide important leads to improve the yield of rice. Co-expression relationships derived from condition-dependent gene expression data is an effective way to identify the functional associations between genes that are part of the same biological process and may be under similar transcriptional control. For this purpose, vast amount of freely available transcriptomic data can be used for functional annotation. In this study we consider gene expression data for different tissues and developmental stages in response to drought stress. We analyze the network of co-expressed genes to identify drought-responsive genes modules in a tissue and stage-specific manner based on differential expression and gene enrichment analysis. Taking cues from the systems-level behavior of these modules, we propose two approaches to identify clusters of tightly co-expressed/co-regulated genes. Using graph-centrality measures and differential gene expression, we identify biologically informative genes that lack any functional annotation. We show that using orthologous information from other plant species, the conserved co-expression patterns of the uncharacterized genes can be identified. Presence of a conserved neighborhood enables us to extrapolate functional annotation. Alternatively, we show that ‘guide-gene’ approach can help in understanding the tissue-specific transcriptional regulation of uncharacterized genes. Finally, we confirm the …

Abstract

In the last decade there has been considerable interest in a novel dynamical phenomenon of chimera states observed in an array of non-locally coupled oscillators where regions of coherence and incoherence coexist across the network. In this study we show how chimera states emerge in coupled logistic maps for certain specified initial conditions when the range and strength of coupling is varied. Here we show that these states are very robust and persist even in the presence of noise in the network parameters. On applying localized external perturbation to the incoherent regions, it is possible to obtain a completely coherent/incoherent dynamics in the whole network depending on the strength and sign of perturbation. This has important applications in the control of undesirable local dynamics, such as seizures in neural systems, or fibrillations in cardiac

Abstract

Protein-protein interaction (PPI) networks are valuable biological source of data which contain rich information useful for protein function prediction. The PPI networks face data quality challenges like noise in the form of false positive edges and incompleteness in the form of missing biologically valued edges. These issues can be handled by enhancing data quality through graph transformations for improved protein function prediction. We proposed an improved method to extract similar proteins based on the notion of relaxed neighborhood. The proposed method can be applied to carry out graph transformation of PPI network data sets to improve the performance of protein function prediction task by adding biologically important protein interactions, removing dissimilar interactions and increasing reliability score of the interactions. By preprocessing PPI network data sets with the proposed methodology, experiment results on both un-weighted and weighted PPI network data sets show that, the proposed methodology enhances the data quality and improves prediction accuracy over other approaches. The results indicate that the proposed approach could utilize underutilized knowledge, such as distant relationships embedded in the PPI graph.