Parallel Implementation of Efficient Search Schemes for the Inference of Cancer Progression Models

The emergence and development of cancer is a consequence of the accumulation over time of genomic mutations involving a specific set of genes, which provides the cancer clones with a functional selective advantage. In this work, we model the order of accumulation of such mutations during the progression, which eventually leads to the disease, by means of probabilistic graphic models, i.e., Bayesian Networks (BNs). We investigate how to perform the task of learning the structure of such BNs, according to experimental evidence, adopting a global optimization meta-heuristics. In particular, in this work we rely on Genetic Algorithms, and to strongly reduce the execution time of the inference -- which can also involve multiple repetitions to collect statistically significant assessments of the data -- we distribute the calculations using both multi-threading and a multi-node architecture. The results show that our approach is characterized by good accuracy and specificity; we also demonstrate its feasibility, thanks to a 84x reduction of the overall execution time with respect to a traditional sequential implementation

Global DNA methylation and transcriptional analyses of human ESC-derived cardiomyocytes.

With defined culture protocol, human embryonic stem cells (hESCs) are able to generate cardiomyocytes in vitro, therefore providing a great model for human heart development, and holding great potential for cardiac disease therapies. In this study, we successfully generated a highly pure population of human cardiomyocytes (hCMs) (>95% cTnT(+)) from hESC line, which enabled us to identify and characterize an hCM-specific signature, at both the gene expression and DNA methylation levels. Gene functional association network and gene-disease network analyses of these hCM-enriched genes provide new insights into the mechanisms of hCM transcriptional regulation, and stand as an informative and rich resource for investigating cardiac gene functions and disease mechanisms. Moreover, we show that cardiac-structural genes and cardiac-transcription factors have distinct epigenetic mechanisms to regulate their gene expression, providing a better understanding of how the epigenetic machinery coordinates to regulate gene expression in different cell types

Large scale homophily analysis in twitter using a twixonomy

In this paper we perform a large-scale homophily analysis on Twitter using a hierarchical representation of users' interests which we call a Twixonomy. In order to build a population, community, or single-user Twixonomy we first associate "topical" friends in users' friendship lists (i.e. friends representing an interest rather than a social relation between peers) with Wikipedia categories. A wordsense disambiguation algorithm is used to select the appropriate wikipage for each topical friend. Starting from the set of wikipages representing "primitive" interests, we extract all paths connecting these pages with topmost Wikipedia category nodes, and we then prune the resulting graph G efficiently so as to induce a direct acyclic graph. This graph is the Twixonomy. Then, to analyze homophily, we compare different methods to detect communities in a peer friends Twitter network, and then for each community we compute the degree of homophily on the basis of a measure of pairwise semantic similarity. We show that the Twixonomy provides a means for describing users' interests in a compact and readable way and allows for a fine-grained homophily analysis. Furthermore, we show that midlow level categories in the Twixonomy represent the best balance between informativeness and compactness of the representation

SLIQ: Simple Linear Inequalities for Efficient Contig Scaffolding

Scaffolding is an important subproblem in "de novo" genome assembly in which mate pair data are used to construct a linear sequence of contigs separated by gaps. Here we present SLIQ, a set of simple linear inequalities derived from the geometry of contigs on the line that can be used to predict the relative positions and orientations of contigs from individual mate pair reads and thus produce a contig digraph. The SLIQ inequalities can also filter out unreliable mate pairs and can be used as a preprocessing step for any scaffolding algorithm. We tested the SLIQ inequalities on five real data sets ranging in complexity from simple bacterial genomes to complex mammalian genomes and compared the results to the majority voting procedure used by many other scaffolding algorithms. SLIQ predicted the relative positions and orientations of the contigs with high accuracy in all cases and gave more accurate position predictions than majority voting for complex genomes, in particular the human genome. Finally, we present a simple scaffolding algorithm that produces linear scaffolds given a contig digraph. We show that our algorithm is very efficient compared to other scaffolding algorithms while maintaining high accuracy in predicting both contig positions and orientations for real data sets.Comment: 16 pages, 6 figures, 7 table