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.

Abstract

In recent studies it has been shown that graph representation of protein structures is capable of capturing the 3-dimensional fold of the protein very well, thus providing a computationally efficient approach for protein structure analysis. Centrality measures are generally used to identify the relative importance of a node in the network. Here we demonstrate a novel application of centrality analysis: to identify tandemly repeated structural motifs in 3-d protein structures. This is done by analyzing the profile of various centrality measures in the repeat region. The comparative analysis of five centrality measures based on local connectivity, shortest paths, principal eigen spectra and feedback centrality is presented on proteins containing contiguous ankyrin structural motifs to identify which centrality measure best captures the repetitive pattern of ankyrin. We observe that principal eigen spectra of the adjacency matrix and Katz status index, both exhibit a distinct profile for the ankyrin motif capturing its characteristic anti-parallel helix-turn-helix fold. No such conserved pattern was observed in the repeat regions of equivalent random networks, suggesting that the conserved pattern arises from the 3d fold of the structural motif.

Abstract

Repetition of a structural motif within protein is associated with a wide range of structural and functional roles. In most cases the repeating units are well conserved at the structural level while at the sequence level, they are mostly undetectable suggesting the need for structure-based methods. Since most known methods require a training dataset, de novo approach is desirable. Here, we propose an efficient graph-based approach for detecting structural repeats in proteins. In a protein structure represented as a graph, interactions between inter- and intra-repeat units are well captured by the eigen spectra of adjacency matrix of the graph. These conserved interactions give rise to similar connections and a unique profile of the principal eigen spectra for each repeating unit. The efficacy of the approach is shown on eight repeat families annotated in UniProt, comprising of both solenoid and nonsolenoid repeats with …

Abstract

Tandem repetition of structural motifs in proteins is frequently observed across all forms of life. Topology of repeating unit and its frequency of occurrence are associated to a wide range of structural and functional roles in diverse proteins, and defects in repeat proteins have been associated with a number of diseases. It is thus desirable to accurately identify specific repeat type and its copy number. Weak evolutionary constraints on repeat units and insertions/deletions between them make their identification difficult at the sequence level and structure based approaches are desired. The proposed graph spectral approach is based on protein structure represented as a graph for detecting one of the most frequently observed structural repeats, Ankyrin repeat.

Abstract

BACKGROUND: Ankyrin repeat is one of the most frequently observed structural motif in proteins across all kingdoms of life. These proteins are involved in diverse set of cellular functions and act as transcriptional initiators, cell-cycle regulators, cytoskeletal, ion transporters and signal transducers, and consequently, defects in ankyrin repeat proteins have been found in a number of human diseases. Identification of these structural repeats at the sequence level is difficult due to low conservation between the repeat copies. Thus, analysis at the structure level is desirable. RESULTS: In this study, we propose a graph based approach in the identification and analysis of ankyrin repeats. The 3-dimensional topology of protein structures has been shown to be well captured by protein contact graphs. The connectivity information of these networks is represented in the adjacency matrix and here we propose the analysis of the eigen spectra of the adjacency matrix in the identification of structural repeats. A clear two-peak pattern corresponding to the helix-turn-helix region of the Ankyrin motif is observed in the principal eigenvector of the adjacency matrix. The length distribution of this repetitive pattern along with the organization of the secondary structure elements is used to design an algorithm to identify the Ankyrin structural motifs. The analysis has been carried out on a non-redundant set of 51 proteins annotated in the UniProt database and a very good agreement is observed. Analysis of all the proteins in the alpha class and alpha+beta class in SCOP database has been performed and a number of novel repeats, not annotated in the database have been identified. This approach is then applied on other structural repeats such as Tetraticopeptide repeat (TPR), Annexin, HEAT, ARM, etc. CONCLUSIONS: The graph based analysis of protein structures, along with domain information such as the organization of the secondary structure architecture provides a computationally efficient approach for the identification of structural repeats.