MOTIVATION: Genome-wide identification of the transcriptomic responses of human cell lines to drug treatments is a challenging issue in medical and pharmaceutical research. However, drug-induced gene expression profiles are largely unknown and unobserved for all combinations of drugs and human cell lines, which is a serious obstacle in practical applications. RESULTS: Here, we developed a novel computational method to predict unknown parts of drug-induced gene expression profiles for various human cell lines and predict new drug therapeutic indications for a wide range of diseases. We proposed a tensor-train weighted optimization (TT-WOPT) algorithm to predict the potential values for unknown parts in tensor-structured gene expression data. Our results revealed that the proposed TT-WOPT algorithm can accurately reconstruct drug-induced gene expression data for a range of human cell lines in the Library of Integrated Network-based Cellular Signatures. The results also revealed that in comparison with the use of original gene expression profiles, the use of imputed gene expression profiles improved the accuracy of drug repositioning. We also performed a comprehensive prediction of drug indications for diseases with gene expression profiles, which suggested many potential drug indications that were not predicted by previous approaches. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

To infer complex structural invariants, shape analyses rely on expressive families of logical properties. Many such analyses manipulate abstract memory states that consist of separating conjunctions of basic predicates describing atomic blocks or summaries. Moreover, they use finite disjunctions of abstract memory states in order to account for dissimilar shapes. Disjunctions should be kept small for the sake of scalability, though precision often requires to keep additional case splits. In this context, deciding when and how to merge case splits and to replace them with summaries is critical both for the precision and for the efficiency. Existing techniques use sets of syntactic rules, which are tedious to design and prone to failure. In this paper, we design a semantic criterion to clump abstract states based on their silhouette which applies not only to the conservative union of disjuncts, but also to the weakening of separating conjunction of memory predicates into inductive summaries. Our approach allows to define union and widening operators that aim at preserving the case splits that are required for the analysis to succeed. We implement this approach in the MemCAD analyzer, and evaluate it on real-world C codes from existing libraries, including programs dealing with doubly linked lists, red-black trees and AVL-trees.

MOTIVATION: Clustering is commonly used to identify the best decoy among many generated in protein structure prediction when using energy alone is insufficient. Calculation of the pairwise distance matrix for a large decoy set is computationally expensive. Typically, only a reduced set of decoys using energy filtering is subjected to clustering analysis. A fast clustering method for a large decoy set would be beneficial to protein structure prediction and this still poses a challenge. RESULTS: We propose a method using propagation of geometric constraints to accelerate exact clustering, without compromising the distance measure. Our method can be used with any metric distance. Metrics that are expensive to compute and have known cheap lower and upper bounds will benefit most from the method. We compared our method's accuracy against published results from the SPICKER clustering software on 40 large decoy sets from the I-TASSER protein folding engine. We also performed some additional speed comparisons on six targets from the 'semfold' decoy set. In our tests, our method chose a better decoy than the energy criterion in 25 out of 40 cases versus 20 for SPICKER. Our method also was shown to be consistently faster than another fast software performing exact clustering named Calibur. In some cases, our approach can even outperform the speed of an approximate method. AVAILABILITY: Our C++ software is released under the GNU General Public License. It can be downloaded from http://www.riken.jp/zhangiru/software/durandal_released.tgz.

UNLABELLED: Bioinformaticians are tackling increasingly computation-intensive tasks. In the meantime, workstations are shifting towards multi-core architectures and even massively multi-core may be the norm soon. Bag-of-Tasks (BoT) applications are commonly encountered in bioinformatics. They consist of a large number of independent computation-intensive tasks. This note introduces PAR, a scalable, dynamic, parallel and distributed execution engine for Bag-of-Tasks. PAR is aimed at multi-core architectures and small clusters. Accelerations obtained thanks to PAR on two different applications are shown. AVAILABILITY: PAR is released under the GNU General Public License version three and can be freely downloaded (http://download.savannah.gnu.org/releases/par/par.tgz).