We present a latent variable model-based approach to the analysis of gene expression patterns, coupled with topographic clustering. Aspect model, a latent variable model for dyadic data, is applied to extract latent patterns underlying complex variations of gene expression levels. Then a topographic clustering is performed to find coherent groups of genes, based on the extracted latent patterns as well as individual gene expression behaviors. Applied to cell cycle regulated genes of the yeast Saccharomyces cerevisiae, the proposed method could discover biologically meaningful patterns related with characteristic expression behavior in particular cell cycle phases. In addition, the display of the variation in the composition of these latent patterns on the cluster map provided more facilitated interpretation of the resulting cluster structure. From this, we argue that latent variable models, coupled with topographic clustering, are a promising tool for explorative analysis of gene expression data.
Cell Cycle ; Cluster Analysis* ; Gene Expression Profiling* ; Gene Expression* ; Saccharomyces cerevisiae ; Yeasts

Local alignment is an important task in molecular biology to see if two sequences contain regions that are similar. The most popular approach to local alignment is the use of dynamic programming due to Smith and Waterman, but the alignment reported by the Smith-Waterman algorithm has some undesirable properties. The recent approach to fix these problems is to use the notion of normalized scores for local alignments by Arslan, Egecioglu and Pevzner. In this paper we consider the problem of finding all local alignments whose normalized scores are above a given threshold, and present a fast heuristic algorithm. Our algorithm is 180-330 times faster than Arslan et al.''s for sequences of length about 120 kbp and about 40-50 times faster for sequences of length about 30 kbp.
Molecular Biology

The analysis of DNA microarry data is one of the most important things for functional genomics research. The matrix representation of microarray data and its successive 'optimal' incisional hyperplanes is a useful platform for developing optimization algorithms to determine the optimal partitioning of pairwise proximity matrix representing completely connected and weighted graph. We developed Deterministic Annealing (DA) approach to determine the successive optimal binary partitioning. DA algorithm demonstrated good performance with the ability to find the 'globally optimal' binary partitions. In addition, the objects that have not been clustered at small non-zero temperature, are considered to be very sensitive to even small randomness, and can be used to estimate the reliability of the clustering.
Cluster Analysis ; DNA* ; Gene Expression* ; Genomics ; Oligonucleotide Array Sequence Analysis*

The latest measure of the relative evolutionary age of protein structure families was applied (based on taxonomic diversity) using the protein structural interactome map (PSIMAP). It confirms that, in general, protein domains, which are hubs in this interaction network, are older than protein domains with fewer interaction partners. We apply a hypothesis of 'biological network evolution' to explain the positive correlation between interaction and age. It agrees to the previous suggestions that proteins have acquired an increasing number of interaction partners over time via the stepwise addition of new interactions. This hypothesis is shown to be consistent with the scale-free interaction network topologies proposed by other groups. Closely co-evolved structural interaction and the dynamics of network evolution are used to explain the highly conserved core of protein interaction pathways, which exist across all divisions of life.
Humans ; Protein Structure, Tertiary

No abstract available.
Computational Biology* ; Genomics* ; Protein Interaction Maps

Helicobacter pylori is a Gram-negative bacteria that is responsible for gastritis in human. Its spiral flagellated body helps in locomotion and colonization in the host environment. It is capable of living in the highly acidic environment of the stomach with the help of acid adaptive genes. The genome of H. pylori 26695 strain contains 1,555 coding genes that encode 1,445 proteins. Out of these, 340 proteins are characterized as hypothetical proteins (HP). This study involves extensive analysis of the HPs using an established pipeline which comprises various bioinformatics tools and databases to find out probable functions of the HPs and identification of virulence factors. After extensive analysis of all the 340 HPs, we found that 104 HPs are showing characteristic similarities with the proteins with known functions. Thus, on the basis of such similarities, we assigned probable functions to 104 HPs with high confidence and precision. All the predicted HPs contain representative members of diverse functional classes of proteins such as enzymes, transporters, binding proteins, regulatory proteins, proteins involved in cellular processes and other proteins with miscellaneous functions. Therefore, we classified 104 HPs into aforementioned functional groups. During the virulence factors analysis of the HPs, we found 11 HPs are showing significant virulence. The identification of virulence proteins with the help their predicted functions may pave the way for drug target estimation and development of effective drug to counter the activity of that protein.
Carrier Proteins ; Clinical Coding ; Colon ; Computational Biology ; Drug Discovery ; Gastritis ; Genome ; Gram-Negative Bacteria ; Helicobacter pylori* ; Helicobacter* ; Humans ; Locomotion ; Sequence Analysis* ; Stomach ; Virulence Factors* ; Virulence*

Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs). Argonaute (AGO) protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism. In the current work, 64 genes and 23 miRNAs have been selected from literatures, whose deregulation is well established in seven types of solid cancer like lung, breast, prostate, pancreases, colorectal, stomach, and bladder cancer. In silico study reveals, miRNAs namely, miR-106a, miR-21, and miR-29b-2 have a strong binding affinity towards PTEN, TGFBR2, and VEGFA genes, respectively, suggested as important factors in RNA silencing mechanism. Furthermore, interaction between AGO protein (PDB ID-3F73, chain A) with selected miRNAs and with miRNAs-mRNAs duplex were studied computationally to understand their binding at molecular level. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding miRNAs based gene silencing mechanism in solid cancer.
Breast ; Computer Simulation* ; Endothelial Cells ; Gene Silencing ; Humans ; Hydrogen Bonding ; Lung ; MicroRNAs* ; Pancreas ; Prostate ; RNA Interference ; RNA, Messenger ; Stomach ; Urinary Bladder ; Urinary Bladder Neoplasms

Zika virus (ZIKV) is a mosquito borne pathogen, belongs to Flaviviridae family having a positive-sense single-stranded RNA genome, currently known for causing large epidemics in Brazil. Its infection can cause microcephaly, a serious birth defect during pregnancy. The recent outbreak of ZIKV in February 2016 in Brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against ZIKV. Amodiaquine, prochlorperazine, quinacrine, and berberine are few promising drugs approved by Food and Drug Administration against dengue virus which also belong to Flaviviridae family. In this study, we performed molecular docking analysis of these drugs against nonstructural 3 (NS3) protein of ZIKV. The protease activity of NS3 is necessary for viral replication and its prohibition could be considered as a strategy for treatment of ZIKV infection. Amongst these four drugs, berberine has shown highest binding affinity of –5.8 kcal/mol and it is binding around the active site region of the receptor. Based on the properties of berberine, more similar compounds were retrieved from ZINC database and a structure-based virtual screening was carried out by AutoDock Vina in PyRx 0.8. Best 10 novel drug-like compounds were identified and amongst them ZINC53047591 (2-(benzylsulfanyl)-3-cyclohexyl-3H-spiro[benzo[h]quinazoline-5,1'-cyclopentan]-4(6H)-one) was found to interact with NS3 protein with binding energy of –7.1 kcal/mol and formed H-bonds with Ser135 and Asn152 amino acid residues. Observations made in this study may extend an assuring platform for developing anti-viral competitive inhibitors against ZIKV infection.
Amodiaquine ; Berberine ; Brazil ; Catalytic Domain ; Congenital Abnormalities ; Culicidae ; Dengue Virus ; Drug Design ; Flaviviridae ; Flavivirus ; Genome ; High-Throughput Screening Assays ; Humans ; Mass Screening* ; Microcephaly ; Molecular Docking Simulation ; Pregnancy ; Prochlorperazine ; Quinacrine ; RNA ; United States Food and Drug Administration ; Zika Virus* ; Zinc

The influenza A (H1N1) virus, also known as swine flu is a leading cause of morbidity and mortality since 2009. There is a need to explore novel anti-viral drugs for overcoming the epidemics. Traditionally, different plant extracts of garlic, ginger, kalmegh, ajwain, green tea, turmeric, menthe, tulsi, etc. have been used as hopeful source of prevention and treatment of human influenza. The H1N1 virus contains an important glycoprotein, known as neuraminidase (NA) that is mainly responsible for initiation of viral infection and is essential for the life cycle of H1N1. It is responsible for sialic acid cleavage from glycans of the infected cell. We employed amino acid sequence of H1N1 NA to predict the tertiary structure using Phyre2 server and validated using ProCheck, ProSA, ProQ, and ERRAT server. Further, the modelled structure was docked with thirteen natural compounds of plant origin using AutoDock4.2. Most of the natural compounds showed effective inhibitory activity against H1N1 NA in binding condition. This study also highlights interaction of these natural inhibitors with amino residues of NA protein. Furthermore, among 13 natural compounds, theaflavin, found in green tea, was observed to inhibit H1N1 NA proteins strongly supported by lowest docking energy. Hence, it may be of interest to consider theaflavin for further in vitro and in vivo evaluation.
Amino Acid Sequence ; Curcuma ; Garlic ; Ginger ; Glycoproteins ; Hope ; In Vitro Techniques ; Influenza A virus ; Influenza A Virus, H1N1 Subtype ; Influenza, Human* ; Life Cycle Stages ; Molecular Docking Simulation ; Mortality ; N-Acetylneuraminic Acid ; Neuraminidase* ; Phytochemicals ; Plant Extracts ; Plants ; Polysaccharides ; Swine ; Tea

Nuclear mitochondrial DNA segment (Numt) insertion describes a well-known phenomenon of mitochondrial DNA transfer into a eukaryotic nuclear genome. However, it has not been well understood, especially in plants. Numt insertion patterns vary from species to species in different kingdoms. In this study, the patterns were surveyed in nine plant species, and we found some tip-offs. First, when the mitochondrial genome size is relatively large, the portion of the longer Numt is also larger than the short one. Second, the whole genome duplication event increases the ratio of the shorter Numt portion in the size distribution. Third, Numt insertions are enriched in exon regions. This analysis may be helpful for understanding plant evolution.
DNA, Mitochondrial* ; Exons ; Genome ; Genome, Mitochondrial ; Plants*