Resolving deconvolution ambiguity in gene alternative splicing

Background  

For many gene structures it is impossible to resolve intensity data uniquely to establish abundances of splice variants. This was empirically noted by Wang et al. in which it was called a "degeneracy problem". The ambiguity results from an ill-posed problem where additional information is needed in order to obtain an unique answer in splice variant deconvolution.     

WholePathwayScope: a comprehensive pathway-based analysis tool for high-throughput data

Background  

Analysis of High Throughput (HTP) Data such as microarray and proteomics data has provided a powerful methodology to study patterns of gene regulation at genome scale. A major unresolved problem in the post-genomic era is to assemble the large amounts of data generated into a meaningful biological context. We have developed a comprehensive software tool, WholePathwayScope (WPS), for deriving biological insights from analysis of HTP data.     

A web-database of mammalian morphology and a reanalysis of placental phylogeny

Background  

Recent publications concerning the interordinal phylogeny of placental mammals have converged on a common signal, consisting of four major radiations with some ambiguity regarding the placental root. The DNA data with which these relationships have been reconstructed are easily accessible from public databases; access to morphological characters is much more difficult. Here, I present a graphical web-database of morphological characters focusing on placental mammals, in tandem with a combined-data phylogenetic analysis of placental mammal phylogeny.     

Performance evaluation of commercial short-oligonucleotide microarrays and the impact of noise in making cross-platform correlations

Background  

Despite the widespread use of microarrays, much ambiguity regarding data analysis, interpretation and correlation of the different technologies exists. There is a considerable amount of interest in correlating results obtained between different microarray platforms. To date, only a few cross-platform evaluations have been published and unfortunately, no guidelines have been established on the best methods of making such correlations. To address this issue we conducted a thorough evaluation of two commercial microarray platforms to determine an appropriate methodology for making cross-platform correlations.     

nuID: a universal naming scheme of oligonucleotides for Illumina, Affymetrix, and other microarrays

Background  

Oligonucleotide probes that are sequence identical may have different identifiers between manufacturers and even between different versions of the same company's microarray; and sometimes the same identifier is reused and represents a completely different oligonucleotide, resulting in ambiguity and potentially mis-identification of the genes hybridizing to that probe.     

Computing paths and cycles in biological interaction graphs

Background  

Interaction graphs (signed directed graphs) provide an important qualitative modeling approach for Systems Biology. They enable the analysis of causal relationships in cellular networks and can even be useful for predicting qualitative aspects of systems dynamics. Fundamental issues in the analysis of interaction graphs are the enumeration of paths and cycles (feedback loops) and the calculation of shortest positive/negative paths. These computational problems have been discussed only to a minor extent in the context of Systems Biology and in particular the shortest signed paths problem requires algorithmic developments.     

Independent component analysis reveals new and biologically significant structures in micro array data

Background  

An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS) problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes.     

Molecular characterisation of drug-resistant Plasmodium falciparum from Thailand

Background  

The increasing levels of Plasmodium falciparum resistance to chloroquine (CQ) in Thailand have led to the use of alternative antimalarials, which are at present also becoming ineffective. In this context, any strategies that help improve the surveillance of drug resistance, become crucial in overcoming the problem.     

An adaptive bin framework search method for a beta-sheet protein homopolymer model

Background  

The problem of protein structure prediction consists of predicting the functional or native structure of a protein given its linear sequence of amino acids. This problem has played a prominent role in the fields of biomolecular physics and algorithm design for over 50 years. Additionally, its importance increases continually as a result of an exponential growth over time in the number of known protein sequences in contrast to a linear increase in the number of determined structures. Our work focuses on the problem of searching an exponentially large space of possible conformations as efficiently as possible, with the goal of finding a global optimum with respect to a given energy function. This problem plays an important role in the analysis of systems with complex search landscapes, and particularly in the context of ab initio protein structure prediction.     

Automatic document classification of biological literature

Background  

Document classification is a wide-spread problem with many applications, from organizing search engine snippets to spam filtering. We previously described Textpresso, a text-mining system for biological literature, which marks up full text according to a shallow ontology that includes terms of biological interest. This project investigates document classification in the context of biological literature, making use of the Textpresso markup of a corpus of Caenorhabditis elegans literature.     

Detecting disease associated modules and prioritizing active genes based on high throughput data

Background  

The accumulation of high-throughput data greatly promotes computational investigation of gene function in the context of complex biological systems. However, a biological function is not simply controlled by an individual gene since genes function in a cooperative manner to achieve biological processes. In the study of human diseases, rather than to discover disease related genes, identifying disease associated pathways and modules becomes an essential problem in the field of systems biology.     

Selecting additional tag SNPs for tolerating missing data in genotyping

Background  

Recent studies have shown that the patterns of linkage disequilibrium observed in human populations have a block-like structure, and a small subset of SNPs (called tag SNPs) is sufficient to distinguish each pair of haplotype patterns in the block. In reality, some tag SNPs may be missing, and we may fail to distinguish two distinct haplotypes due to the ambiguity caused by missing data.     

Automation of gene assignments to metabolic pathways using high-throughput expression data

Background  

Accurate assignment of genes to pathways is essential in order to understand the functional role of genes and to map the existing pathways in a given genome. Existing algorithms predict pathways by extrapolating experimental data in one organism to other organisms for which this data is not available. However, current systems classify all genes that belong to a specific EC family to all the pathways that contain the corresponding enzymatic reaction, and thus introduce ambiguity.     

Incorporation of gene-specific variability improves expression analysis using high-density DNA microarrays

Background  

The assessment of data reproducibility is essential for application of microarray technology to exploration of biological pathways and disease states. Technical variability in data analysis largely depends on signal intensity. Within that context, the reproducibility of individual probe sets has not been hitherto addressed.     

eGIFT: Mining Gene Information from the Literature

Background  

With the biomedical literature continually expanding, searching PubMed for information about specific genes becomes increasingly difficult. Not only can thousands of results be returned, but gene name ambiguity leads to many irrelevant hits. As a result, it is difficult for life scientists and gene curators to rapidly get an overall picture about a specific gene from documents that mention its names and synonyms.     

RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry

Background  

Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L < N), the consecutive windows folding problem is to compute the minimal free energy (MFE) for the folding of each of the L-sized substrings of S. The consecutive windows folding problem can be naively solved in O(NL³) by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL²) solution for this problem has been described.     

SBEAMS-Microarray: database software supporting genomic expression analyses for systems biology

Background  

The biological information in genomic expression data can be understood, and computationally extracted, in the context of systems of interacting molecules. The automation of this information extraction requires high throughput management and analysis of genomic expression data, and integration of these data with other data types.