DNAV: A WebGL Based Tool for Visualizing the Twists and Turns in the Human Genome

The human genome is tightly folded to fit within the restricted space of the nucleus. One of the key goals in understanding the folding principles of DNA is to unravel the mysteries of how functional elements that are separated from each other are brought together. Long-range interactions between folded segments of chromosomes form complex three-dimensional networks and are fundamental in controlling gene expression. These long-range interactions have been observed using chromosome conformation capture (3C). This Hi-C data contains a wealth of information on the nearest-neighbor influence on the deviation of the DNA axis that can be modeled theoretically. We have developed a tool using WebGL to visualize the modeled structures

Differential binding of RNA polymerase to the wild type Mu mom promoter and its C independent mutant: a theoretical analysis

Using the theoretical model for DNA bending we have analyzed the Mu mom promoter wild type and its mutant tin7 which showed differential binding to the RNA polymerase. We have demonstrated here the structural change as a result of the point mutation which may be responsible for the altered binding of RNA polymerase. Analysis using both sets of parameters essentially gives the same result

Application of artificial neural networks for prokaryotic transcription terminator prediction

Artificial neural networks (ANN) to predict terminator sequences, based on a feed-forward architecture and trained using the error back propagation technique, have been developed. The network uses two different methods for coding nucleotide sequences. In one the nucleotide bases are coded in binary while the other uses the electron-ion interaction potential values (EIIP) of the nucleotide bases. The latter strategy is new, property based and substantially reduces the network size. The prediction capacity of the artificial neural network using both coding strategies is more than 95%

Characterization of the yeast ionome: a genome-wide analysis of nutrient mineral and trace element homeostasis in Saccharomyces cerevisiae

BACKGROUND: Nutrient minerals are essential yet potentially toxic, and homeostatic mechanisms are required to regulate their intracellular levels. We describe here a genome-wide screen for genes involved in the homeostasis of minerals in Saccharomyces cerevisiae. Using inductively coupled plasma-atomic emission spectroscopy (ICP-AES), we assayed 4,385 mutant strains for the accumulation of 13 elements (calcium, cobalt, copper, iron, potassium, magnesium, manganese, nickel, phosphorus, selenium, sodium, sulfur, and zinc). We refer to the resulting accumulation profile as the yeast 'ionome'. RESULTS: We identified 212 strains that showed altered ionome profiles when grown on a rich growth medium. Surprisingly few of these mutants (four strains) were affected for only one element. Rather, levels of multiple elements were altered in most mutants. It was also remarkable that only six genes previously shown to be involved in the uptake and utilization of minerals were identified here, indicating that homeostasis is robust under these replete conditions. Many mutants identified affected either mitochondrial or vacuolar function and these groups showed similar effects on the accumulation of many different elements. In addition, intriguing positive and negative correlations among different elements were observed. Finally, ionome profile data allowed us to correctly predict a function for a previously uncharacterized gene, YDR065W. We show that this gene is required for vacuolar acidification. CONCLUSION: Our results indicate the power of ionomics to identify new aspects of mineral homeostasis and how these data can be used to develop hypotheses regarding the functions of previously uncharacterized genes

Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells

Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations

On Selecting mRNA Isoform Features for Profiling Prostate Cancer

Alternative splicing of human pre-mRNA is a very common phenomenon and is a major contributor to proteome diversity. mRNA isoforms that arise as a result of alternative splicing also provide a more complete picture of the transcriptome as they reflect the additional processing a pre-mRNA undergoes before being translated into a functional product. It has been reported that molecular alterations of cells can occur as a result of the differential expression of mRNA isoforms, resulting in cancerous or normal tissue. Quantification of mRNA isoforms can thus be used as a better indicator in distinguishing a normal tissue from a cancerous tissue. In our earlier study we had used mRNA isoforms expression to identify biomarkers for prostate cancer (Li et. al, 2006. Cancer Res. 66 (8) 4079–4088). Here we have used statistical methods of multiple comparison and have developed a simple scoring scheme to extract isoform features. Further, we have rigorously analyzed the isoform expression data to understand the variability and heterogeneity associated with the expression levels between (i) prostate cancer cell lines and non-prostate cancer cell lines and (ii) normal prostate tissue and prostate cancer tissue. We found that there were several isoforms that showed significant difference in expression within the same class. We were also able to successfully identify isoforms with similar changes in expression levels, that when used as features for classification was able to provide robust class separation. The features selected using the multiple comparison methods had subsets that were common and disparate with those that were selected using statistical t-tests. This reveals the importance of selecting features using a combination of complementary methods. Keywords: mRNA isoforms, Splicing arrays, Multiple comparison, Prostate cance

On the consensus structure within the E. coli promoters

Using the theoretical model of DNA curvature, we have studied about 112 different E. coli promoters with a view to obtain some common super structures associated with them. Out of the 112 promoters analyzed by theoretical gel electrophoresis permutation about 66 of them have their minima lying between the - 10 and the -35 region. The analysis of the bases at the minima reveals strong structural similarities. The differences can account for the varying strengths of the promoters as well as for different degree with which the RNA polymerase binds to these regions. The effects of mutation in each of these 112 promoters and their changes in curvature dispersion have also been evaluated

Differential binding of RNA polymerase to the wild type Mu mom promoter and its C independent mutant: a theoretical analysis

Using the theoretical model for DNA bending we have analyzed the Mu mom promoter wild type and its mutant tin7 which showed differential binding to the RNA polymerase.We have demonstrated here the structural change as a result of the point mutation which may be responsible for the altered binding of RNA polymerase. Analysis using both sets of parameters essentially gives the same result

Theoretical permutation gel electrophoretic analysis of a curved DNA fragment located in circular permutation

Using the theoretical model for DNA curvature, we analyzed a set of fragments with a curved insert located in circular permutation. The theoretical permutation analysis of each of the cyclically located fragments reveals the presence of a shifting molecular bend locus. The delineation of the molecular bend locus associated with the fragments obtained by a second permutation helps in providing an explanation for the differential mobility behavior of the fragments