Computational Biology

Simulations demonstrate a simple network to be sufficient to control branch point selection, smooth muscle and vasculature formation during lung branching morphogenesis

by Denis Menshykau

G´eraldine Celli`ere, Denis Menshykau, Dagmar Iber
BiologyOpen in press

Proper lung functioning requires not only a correct structure of the conducting airway tree, but also the... more Proper lung functioning requires not only a correct structure of the conducting airway tree, but also the simultaneous
development of smooth muscles and vasculature. Lung branching morphogenesis is strongly stereotyped and
involves the recursive use of only three modes of branching. We have previously shown that the experimentally
described interactions between Fibroblast growth factor (FGF)10, Sonic hedgehog (SHH) and Patched (Ptc) can
give rise to a Turing mechanism that not only reproduces the experimentally observed wildtype branching pattern,
but also, in part counterintuitive, patterns in mutant mice. Here we show that, even though many proteins affect
smooth muscle formation and the expression of Vegfa, an inducer of blood vessel formation, it is sufficient to add
FGF9 to the FGF10/SHH/Ptc module to successfully predict simultaneously the emergence of smooth muscles in
the clefts between growing lung buds, and Vegfa expression in the distal sub-epithelial mesenchyme. Our model
reproduces the phenotype of both wildtype and relevant mutant mice, as well as the results of most culture conditions
described in the literature.

Modeling HIV-1 intracellular replication: two simulation approaches

by Shayan Shahand

N. Zarrabi, E. Mancini, J. Tay, S. Shahand, and P. M. A. Sloot. Procedia Computer Science, 2010.

Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune... more Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular replication where infected cells undergo a single cycle of virus replication. A cell is modeled as an individual entity with certain states and properties. The model is stochastic and keeps track of the main viral proteins and genetic materials inside the cell. Two simulation approaches are used for implementing the model: rate-based and diffusion-based approaches. The results of the simulation are discussed based on the number of integrated viral cDNA and the number of viral mRNA transcribed after a single round of replication. The model is validated by comparing simulation results with available experimental data. Simulation results give insights about the details of HIV replication dynamics inside the cell at the protein level. Therefore the model can be used for future studies of HIV intracellular replication in vivo and drug treatment.

Structural analysis and stochastic modelling suggest a mechanism for calmodulin trapping by CaMKII

by Melanie Stefan

Ten simple rules for getting help from online scientific communities

by Melanie Stefan

Phylogenetic Analysis of the Malaysian Rhinolopus and Hipposideros using mtDNA cytochrome b gene. PJTAS 34(2):281-294.

by M.T. Abdullah, PhD

Read Abdullah (2003)

The phylogenetic relationships among 10 species of Rhinolophus and 10 species of Hipposideros from Borneo and... more The phylogenetic relationships among 10 species of Rhinolophus and 10 species of Hipposideros from Borneo and Peninsular Malaysia were successfully inferred from the partial mitochondrial DNA (mtDNA) cytochrome (cyt) b sequences. Of the 413 nucleotide positions examined, there were 171 positions (41.4%), of which 164 positions (95.9%) were parsimoniously informative. The phylogenetic trees reconstruction using neighbour-joining (NJ), unweighted maximum parsimony (MP) and maximum likelihood (ML) methods suggest the monophyletic clustering of these families. The interspecific relationships within Rhinolophidae were completely resolved, while those within Hipposideridae were not fully resolved, as supported by the low bootstrap values. Overall, the phylogenetic analysis using partial mtDNA cyt b gene was useful to discriminate these complicated taxa and successfully revealed the misidentification of several specimens before due to their similar morphologies.

Keywords: Cytochrome b, Hipposideros, mitochondrial DNA, phylogenetics, Rhinolophus

Morphometrical Variations of Malaysian Hipposideros Species. 2012

by M.T. Abdullah, PhD

Read Vijaya et al (2012)

A study on the morphometrical variations among four Malaysian Hipposideros species was conducted using voucher... more A study on the morphometrical variations among four Malaysian Hipposideros species was conducted using voucher specimens deposited in Universiti Malaysia Sarawak (UNIMAS) Zoological Museum and the Department of Widlife and National Park (DWNP) Kuala Lumpur. Twenty two individuals from four species of Hipposideros ater, H. bicolor, H. cineraceus and H. dyacorum were morphologically measured, in which a total of 27 linear parameters of body, skull and dentals of each were appropriately recorded. The statistical data were later subjected to discriminant function analysis (DFA) and canonical variate analysis (CVA) using SPSS version 15.0 and unweighted pair-group method average (UPGMA) cluster analysis using Minitab version 14.4. The highest character loadings observed in Function l, Function 2 and Function 3 were the forearm length (FA), the third digit second phalanx length (D3P2L) and the palatal length (PL) with standardised canonical discriminant function coefficient values of 21.910, 5.770 and 5.095, respectively. These three characters were identified as the best diagnostic features for discriminating these closely related species of Hipposideros. Hence, this morphometric approach could be a promising tool as an alternative to the molecular
DNA analysis for identification of Chiroptera species.

Phylogeny and Phylogeography of insect bat Myotis muricola. 2012

by M.T. Abdullah, PhD

http://scholar.google.com.my/citations?hl=en&user=ylnvJSAAAAAJ

Myotis muricola is a widespread species covering the Malay Archipelago through the West and East of Wallace’s Line.... more Myotis muricola is a widespread species covering the Malay Archipelago through the West and East of Wallace’s Line. The genetic analysis, based on partial cytochrome b gene, shows the high genetic variation within M. muricola. The phylogenetic analysis has indicated that M. muricola in the Malay Archipelago are monophyletic. Members of M. muricola Eastern are grouped together independently of M. muricola Western and both groups are distantly related. On the other hand, M. muricola Western and M. muricola Eastern are distinct species and sister taxa to M. mystacinus. Based on the high genetic distance (26.8% to 38.5%) and the Genetic Species Concept (Baker & Bradley, 2006), it can be concluded that M. muricola Western and M. muricola Eastern should be considered as two distinct species. Furthermore, two subgroups within M. muricola Western, namely Sumatra-Asian and Bornean subgroups, are recognised as distinct subspecies (with genetic distance of 5.1% to 10.8%). The evidence from the molecular data indicated M. muricola Eastern as the ancestor of M. muricola species complex in the Malay Archipelago, which had earlier diverged into the western region during the Pliocene. Meanwhile, the geographical conditions during the Pleistocene had given more chances for fauna to diversify. It was predicted that M. muricola diverged in the western part of the Malay Archipelago during the Pleistocene when the sea level dropped and produced some landbridges among the islands in Sundaland. The hypothetical dispersal routes of M. muricola are related to the ancient Sunda River systems that produced gallery forest corridors for migration and which served as Pleistocene
refuges during the migration.

Phylogeny and Phylogeography of insect bat Myotis muricola (Gray, 1846) (Chiroptera: Vespertilionidae) from the West and and East of Wallace's Line Inferred from Partial MtDNA Cytochrome b Gene. Sigit Wiantoro, Ibnu Maryanto and M.T. Abdullah. 2012. Pertanika Journal of Tropical Agricultural Science 35(2): 271-292.

Malaysian fruit bats phylogeny inferred using ribosomal RNA. Ryan, J.R., K.H.G. Andy, V.K. Jayaraj, Y. Esa, A.A. Sallehin and Abdullah, M.T. 2008. Pertanika Journal of Tropical Agricultural Science 31(1):107-117. (SCOPUS-Cited Publication).

by M.T. Abdullah, PhD

Fourteen species of the Malaysian fruit bats (Pteropodidae) were used in this DNA taxonomy using 1,334bp of the 12S... more Fourteen species of the Malaysian fruit bats (Pteropodidae) were used in this DNA taxonomy using 1,334bp of the 12S ribosomal RNA (rRNA), transfer RNA (tRNA) valine and 16S rRNA gene segments. Previous studies using DNA found contradictions between morphology and molecular data in inferring the phylogeny of the fruit bats proposed by Andersen (1912). Our phylogenetic analysis using the neighbor-joining and the maximum parsimony methods did not support the monophyly of the subfamily Macroglossinae and the cynopterine group of the subfamily Pteropodinae as proposed by classical taxonomists. This is congruent with previous molecular studies. Here, we provide the first registered 12S rRNA, tRNA valine and 16S rRNA sequence records for Dyacopterus spadiceus in the GenBank database. This study represents the first attempt to infer the phylogenetic relationship of fruit bats from Malaysia using molecular methods.

Molecular phylogenetics and systematics of five genera of Malaysian murine rodents (Maxomys, Sundamys, Leopoldamys, Niviventer and Rattus) inferred from partial mitochondrial cytochrome c oxidase subunit I (COI) gene.

by M.T. Abdullah, PhD

Nur Aida Md Tamrin and M. T. Abdullah. 2011. Journal of Science and Technology in the Tropics 7: 75-86. (SCOPUS-indexed).

We genetically analysed 50 specimens of Murinae from Peninsular Malaysia and Sarawak, assigned to 12 species.... more We genetically analysed 50 specimens of Murinae from Peninsular Malaysia and Sarawak, assigned to 12 species. Phylogenetic analyses of partial mitochondrial cytochrome c oxidase subunit I (476 base pairs) using four methods, namely, neighbour-joining (NJ), maximum parsimony (MP), maximum likelihood (ML) and Bayesian method resulted in similar statistically supported clades with minimal change in branching order. The analyses discovered that there were intermediate form of Maxomys species within M. whiteheadi and M. ochraceiventer populations. They display same external morphology as M. whiteheadi but genetically closer to M. ochraceiventer. Craniodental measurements showed significant differences between the three populations. Rattus and Sundamys appeared not fully resolved while Leopoldamys and Niviventer were steadily clustered. The intraspecific geographic variation in some species agrees with previous studies on the vicariance scenario and diversification of flora and fauna in Malaysia and Borneo.

Nur Aida Md Tamrin and M. T. Abdullah. 2011. Journal of Science and Technology in the Tropics 7: 75-86. (SCOPUS-indexed).

Probes containing runs of guanines provide insights into the biophysics and bioinformatics of Affymetrix GeneChips

by Andrew Harrison

Evolving Regular Expressions for GeneChip Probe Performance Prediction

by Andrew Harrison

Creating regular expressions as mRNA motifs with GP to predict human exon splitting

by Andrew Harrison

RNAnet a Map of Human Gene Expression

by Andrew Harrison

LOX: Inferring Level of Expression From Diverse Methods of Census Sequencing

by Jeffrey Townsend

We present LOX (Level Of eXpression) that estimates the Level Of gene eXpression from high-throughput-expressed... more We present LOX (Level Of eXpression) that estimates the Level Of gene eXpression from high-throughput-expressed sequence datasets with multiple treatments or samples. Unlike most analyses, LOX incorporates a gene bias model that facilitates integration of diverse transcriptomic sequencing data that arises when transcriptomic data have been produced using diverse experimental methodologies. LOX integrates overall sequence count tallies normalized by total expressed sequence count to provide expression levels for each gene relative to all treatments as well as Bayesian credible intervals.

Bayesian Analysis of Gene Expression Levels: Statistical Quantification of Relative MRNA Level Across Multiple Strains or Treatments

by Jeffrey Townsend

BACKGROUND: Methods of microarray analysis that suit experimentalists using the technology are vital. Many... more BACKGROUND: Methods of microarray analysis that suit experimentalists using the technology are vital. Many methodologies discard the quantitative results inherent in cDNA microarray comparisons or cannot be flexibly applied to multifactorial experimental design. Here we present a flexible, quantitative Bayesian framework. This framework can be used to analyze normalized microarray data acquired by any replicated experimental design in which any number of treatments, genotypes, or developmental states are studied using a continuous chain of comparisons. RESULTS: We apply this method to Saccharomyces cerevisiae microarray datasets on the transcriptional response to ethanol shock, to SNF2 and SWI1 deletion in rich and minimal media, and to wild-type and zap1 expression in media with high, medium, and low levels of zinc. The method is highly robust to missing data, and yields estimates of the magnitude of expression differences and experimental error variances on a per-gene basis. It reveals genes of interest that are differentially expressed at below the twofold level, genes with high 'fold-change' that are not statistically significantly different, and genes differentially regulated in quantitatively unanticipated ways. CONCLUSIONS: Anyone with replicated normalized cDNA microarray ratio datasets can use the freely available MacOS and Windows software, which yields increased biological insight by taking advantage of replication to discern important changes in expression level both above and below a twofold threshold. Not only does the method have utility at the moment, but also, within the Bayesian framework, there will be considerable opportunity for future development.

Maximum-Likelihood Model Averaging to Profile Clustering of Site Types Across Discrete Linear Sequences

by Jeffrey Townsend

A major analytical challenge in computational biology is the detection and description of clusters of specified site... more A major analytical challenge in computational biology is the detection and description of clusters of specified site types, such as polymorphic or substituted sites within DNA or protein sequences. Progress has been stymied by a lack of suitable methods to detect clusters and to estimate the extent of clustering in discrete linear sequences, particularly when there is no a priori specification of cluster size or cluster count. Here we derive and demonstrate a maximum likelihood method of hierarchical clustering. Our method incorporates a tripartite divide-and-conquer strategy that models sequence heterogeneity, delineates clusters, and yields a profile of the level of clustering associated with each site. The clustering model may be evaluated via model selection using the Akaike Information Criterion, the corrected Akaike Information Criterion, and the Bayesian Information Criterion. Furthermore, model averaging using weighted model likelihoods may be applied to incorporate model uncertainty into the profile of heterogeneity across sites. We evaluated our method by examining its performance on a number of simulated datasets as well as on empirical polymorphism data from diverse natural alleles of the Drosophila alcohol dehydrogenase gene. Our method yielded greater power for the detection of clustered sites across a breadth of parameter ranges, and achieved better accuracy and precision of estimation of clusters, than did the existing empirical cumulative distribution function statistics.

PhyDesign: an online application for profiling phylogenetic informativeness

by Jeffrey Townsend

Background

The rapid increase in number of sequenced genomes for species across of the tree of life is... more Background

The rapid increase in number of sequenced genomes for species across of the tree of life is revealing a diverse suite of orthologous genes that could potentially be employed to inform molecular phylogenetic studies that encompass broader taxonomic sampling. Optimal usage of this diversity of loci requires user-friendly tools to facilitate widespread cost-effective locus prioritization for phylogenetic sampling. The Townsend (2007) phylogenetic informativeness provides a unique empirical metric for guiding marker selection. However, no software or automated methodology to evaluate sequence alignments and estimate the phylogenetic informativeness metric has been available.


Results

Here, we present PhyDesign, a platform-independent online application that implements the Townsend (2007) phylogenetic informativeness analysis, providing a quantitative prediction of the utility of loci to solve specific phylogenetic questions. An easy-to-use interface facilitates uploading of alignments and ultrametric trees to calculate and depict profiles of informativeness over specified time ranges, and provides rankings of locus prioritization for epochs of interest.


Conclusions

By providing these profiles, PhyDesign facilitates locus prioritization increasing the efficiency of sequencing for phylogenetic purposes compared to traditional studies with more laborious and low capacity screening methods, as well as increasing the accuracy of phylogenetic studies. Together with a manual and sample files, the application is freely accessible at http://phydesign.townsend.yale.edu webcite.

The iPlant collaborative: cyberinfrastructure for plant biology

by Naim Matasci

The iPlant Collaborative (iPlant) is a United States National Science Foundation (NSF) funded project that aims to... more The iPlant Collaborative (iPlant) is a United States National Science Foundation (NSF) funded project that aims to create an innovative, comprehensive, and foundational cyberinfrastructure in support of plant biology research (PSCIC, 2006). iPlant is developing cyberinfrastructure that uniquely enables scientists throughout the diverse fields that comprise plant biology to address Grand Challenges in new ways, to stimulate and facilitate cross-disciplinary research, to promote biology and computer science research interactions, and to train the next generation of scientists on the use of cyberinfrastructure in research and education. Meeting humanity’s projected demands for agricultural and forest products and the expectation that natural ecosystems be managed sustainably will require synergies from the application of information technologies. The iPlant cyberinfrastructure design is based on an unprecedented period of research community input, and leverages developments in high-performance computing, data storage, and cyberinfrastructure for the physical sciences. iPlant is an open-source project with application programming interfaces that allow the community to extend the infrastructure to meet its needs. iPlant is sponsoring community-driven workshops addressing specific scientific questions via analysis tool integration and hypothesis testing. These workshops teach researchers how to add bioinformatics tools and/or datasets into the iPlant cyberinfrastructure enabling plant scientists to perform complex analyses on large datasets without the need to master the command-line or high-performance computational services.

A Comprehensive Computational Model to Simulate Transcription Factor Binding in Prokaryotes.

by Nicolae Radu Zabet

A Comprehensive Computational Model to Simulate Transcription Factor Binding in Prokaryotes. Nicolae Radu Zabet and Boris Adryan In Information Processign in Cells and Tissues, volume 7223, pages 35-37. Springer Berlin / Heidelberg, Lecture Notes in Computer Science, 2012, doi:10.1007/978-3-642-28792-3_6.

Site specific transcription factors (TF) are proteins that orchestrate transcription by binding to specific target... more Site specific transcription factors (TF) are proteins that orchestrate transcription by binding to specific target sites on the DNA. This binding can be both sequence- and conformation-specific. However, also non-specific binding with lower affinity can be observed [3]. The number of specific target sites is significantly smaller compared to the number of non-specific sites and, consequently, TF molecules bind, in a first instance, non-specifically to the DNA. Once bound to the DNA the TF molecules perform an one dimensional random walk on the DNA until they either find a target site or unbind from the DNA template. In particular, during the one dimensional random walk on the DNA, a molecule will perform one of the three types of movements: (i) sliding , (ii) hopping and (iii) jumping [6]. This combination of one and three dimensional diffusion is called facilitated diffusion and it is hypothesised that this speeds up the search process [3,2,5].

GRiP: a computational tool to simulate transcription factor binding in prokaryotes

by Nicolae Radu Zabet

GRiP: a computational tool to simulate transcription factor binding in prokaryotes. Nicolae Radu Zabet and Boris Adryan. Bioinformatics, , 28 (9): 1287-1289, 2012, doi:10.1093/bioinformatics/bts132.

Motivation: Transcription factors (TFs) are proteins that regulate gene activity by binding to specific sites on the... more Motivation: Transcription factors (TFs) are proteins that regulate gene activity by binding to specific sites on the DNA. Understanding the way these molecules locate their target site is of great importance in understanding gene regulation. We developed a comprehensive computational model of this process and estimated the model parameters in (Zabet and Adryan, 2011).

Results: GRiP is a highly versatile implementation of this model and simulates the search process in a computationally efficient way. This program aims to provide researchers in the field with a flexible and highly customisable simulation framework. Its features include representation of DNA sequence, TFs and the interaction between TFs and the DNA (facilitated diffusion mechanism), or between various TFs (cooperative behaviour). The software will record both information on the dynamics associated with the search process (locations of molecules) and also steady state results (affinity landscape, occupancy-bias, collision hotspots).

Availability: http://logic.sysbiol.cam.ac.uk/grip

Supplementary information: Additional information and data is presented in the Supplementary Material which is available at Bioinformatics online.