International Journal of Computational Biology and Drug Design

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) based on 3D-QSAR (3D-quantitative structure activity relationship) studies were carried out on 97 flavonoid derivatives as potent P56(lck) protein tyrosine kinase inhibitors. The best prediction was obtained with CoMFA standard model (q² = 0.838, r² = 0.948) using steric, electrostatic along with CoMSIA standard model (q² = 0.714, r² = 0.921) using steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields...

This paper presents a method of separating cells that are connected to each other forming clusters. The difference to many other publications covering similar topics is that the cell types we are dealing with form clusters of highly varying morphology. An advantage of our method is that it can be universally used for different cell types. The segmentation method is based on a growth simulation starting from the nuclei areas. To start the evaluation, the cells need to be made visible with a histological stain, in our case with the May-Grünwald solution...

The chemical universe of molecules reachable from a set of start compounds by iterative application of a finite number of reactions is usually so vast, that sophisticated and efficient exploration strategies are required to cope with the combinatorial complexity. A stringent analysis of (bio)chemical reaction networks, as approximations of these complex chemical spaces, forms the foundation for the understanding of functional relations in Chemistry and Biology. Graphs and graph rewriting are natural models for molecules and reactions...

Microbes play an important role on human health, however, little is known on microbes in the past decades for the limitation of culture-based techniques. Recently, with the development of next-generation sequencing (NGS) technologies, it is now possible to sequence millions of sequences directly from environments samples, and thus it supplies us a sight to probe the hidden world of microbial communities and detect the associations between microbes and diseases. In the present work, we proposed a supervised learning-based method to mine the relationship between microbes and periodontitis with 16S rRNA sequences...

High throughput bacterial RNA-Seq experiments can generate extremely high and imbalanced sequencing coverage. Over- or under-estimation of gene expression levels will hinder accurate gene differential expression analysis. Here we evaluated strategies to identify expression differences of genes with high coverage in bacterial transcriptome data using either raw sequence reads or unique reads with duplicate fragments removed. In addition, we proposed a generalised linear model (GLM) based approach to identify imbalance in read coverage based on sequence compositions...

Differential expression has been a standard tool for analysing case-control transcriptomic data since the advent of microarray technology. It has proved invaluable in characterising the molecular mechanisms of disease. Nevertheless, the expression profile of a gene across samples can be perturbed in ways that leave the expression level unaltered, while a biological effect is nonetheless present. This paper describes and analyses differential Shannon entropy and differential coefficient of variation, two alternate techniques for identifying genes of interest...

The GC-rich bacterial species, Aeromonas salmonicida, is parasitised by both GC-rich phages (Aeromonas phages - phiAS7 and vB_AsaM-56) and GC-poor phages (Aeromonas phages - 25, 31, 44RR2.8t, 65, Aes508, phiAS4 and phiAS5). Both the GC-rich Aeromonas phage phiAS7 and Aeromonas phage vB_AsaM-56 have nearly identical codon usage bias as their host. While all the remaining seven GC-poor Aeromonas phages differ dramatically in codon usage from their GC-rich host. Here, we investigated whether tRNA encoded in the genome of Aeromonas phages facilitate the translation of phage proteins...

In this paper, we introduce an active contour based scheme to localise Drosophila embryos in RGB images. An active contour (initiated as a closed one) maybe converge to an open contour, e.g., in the case that a targeting embryo is touched by a neighbouring one. We propose an algorithmic strategy to detect and restore open active contours. The experiment results show the promise of the proposed scheme.

Topological analysis of protein-protein interaction (PPI) networks has been widely applied to the investigation on cancer mechanisms. However, there is still a debate on whether cancer proteins exhibit more topological centrality compared to the other proteins in the human PPI network. To resolve this debate, we first identified four sets of human proteins, and then mapped these proteins into the yeast PPI network by homologous genes. Finally, we compared these proteins' properties in human and yeast PPI networks...

Bayesian-like operational taxonomic unit examiner (BOTUX) is a new tool for the classification of 16S rRNA gene sequences into operational taxonomic units (OTUs) that addresses the problem of overestimation caused by errors introduced during PCR amplification and DNA sequencing steps. BOTUX utilises a grammar-based assignment strategy, where Bayesian models are built from each word of a given length (e.g., 8-mers). de novo analysis is possible with BOTUX as it does not require a training set, and updates probabilistic models as new sequences are recruited to an OTU...

Using a unique combination of visual, statistical, and data mining methods, we tested the hypothesis that an immune cell's movement pattern can convey key information about the cell's function, antigen specificity, and environment. We applied clustering, statistical tests, and a support vector machine (SVM) to assess our ability to classify different datasets of imaged flouresently labelled T cells in mouse liver. We additionally saw clusters of different movement patterns of T cells of identical antigenic specificity...

MicroRNAseq (miRNAseq) is a form of RNAseq technology that has become an increasingly popular alternative to miRNA expression profiling. Unlike messenger RNA (mRNA), miRNA extraction can be difficult, and sequencing such small RNA can also be problematic. We designed a study to test the reproducibility of miRNAseq technology and the performance of the two popular miRNA isolation methods, mirVana and TRIzol, by sequencing replicated samples using microRNA isolated with each kit. Through careful analysis of our data, we found excellent repeatability of miRNAseq technology...

No abstract text is available yet for this article.

MIA (Melanoma Inhibitory Activity) protein is over expressed in melanoma cells and binds to extracellular matrix proteins as well as to several integrins. These interactions were suggested to promote formation of metastasis. Therefore, abrogation of MIA interaction with other proteins using small molecules might show a diminishing effect on cancer cell invasion. The present study is aimed at the analysis of the integrin-binding site of MIA using molecular docking, followed by a virtual screening for drug-like compounds that show potential as putative inhibitors of MIA-integrin interaction...

Biologists have been investigating plant defence response to virus infections; however, a comprehensive mathematical model of this complex process has not been developed. One obstacle in developing a dynamic model, useful for simulation, is the lack of kinetic data from which the model parameters could be determined. We address this problem by proposing a methodology for iterative improvement of the model parameters until the simulation results come close to the expectation of biology experts. These expectations are formalised in the form of constraints to be satisfied by the model simulations...

MicroRNAs are small (approx. 22nt) non-coding RNAs that regulate the expression of genes by either degrading messenger-RNA (mRNA) that has already been transcribed or by repressing the translation of mRNA, thus inhibiting protein production. This mechanism of gene regulation by binding of the miRNA to 3-prime-untranslated region of target mRNAs has been recently discovered. This sequence-specific post-transcriptional gene regulation process affects large set of genes involved in number of biological pathways...

Many types of clustering techniques for chemical structures have been used in the literature, but it is known that any single method will not always give the best results for all types of applications. Recent work on consensus clustering methods is motivated because of the successes of combining multiple classifiers in many areas and the ability of consensus clustering to improve the robustness, novelty, consistency and stability of individual clusterings. In this paper, the Cluster-based Similarity Partitioning Algorithm (CSPA) was examined for improving the quality of chemical structures clustering...

Augmented path eccentric connectivity topochemical indices (reported in part-1 of the manuscript) along with 42 diverse non-correlating molecular descriptors (shortlisted from a large pool of 2D and 3D MDs) were successfully utilised for the development of models through decision tree, random forest and moving average analysis for the prediction of antitubercular activity of aza and diazabiphenyl analogues of active compound (6S)-2-Nitro-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3] oxazine (PA-824)...

Sample size determination is an important issue in the experimental design of biomedical research. Because of the complexity of RNA-seq experiments, however, the field currently lacks a sample size method widely applicable to differential expression studies utilising RNA-seq technology. In this report, we propose several methods for sample size calculation for single-gene differential expression analysis of RNA-seq data under Poisson distribution. These methods are then extended to multiple genes, with consideration for addressing the multiple testing problem by controlling false discovery rate...

P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in mammalian cells for endogenous and exogenous chemical compounds. However, despite the extensive characterisation of P-gp potential interaction with drug-like molecules, the interaction of carbon nanoparticles with this type of protein molecule is poorly understood. Thus, carbon nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70), capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp interactions using different molecular docking techniques, such as gradient optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and shape-based approach (PatchDock) to estimate the binding affinities between these structures...