We present a new de novo transcriptome assembler, Bridger, which takes advantage of techniques employed in Cufflinks to overcome limitations of the existing de novo assemblers. When tested on dog, human, and mouse RNA-seq data, Bridger assembled more full-length reference transcripts while reporting considerably fewer candidate transcripts, hence greatly reducing false positive transcripts in comparison with the state-of-the-art assemblers. It runs substantially faster and requires much less memory space than most assemblers. More interestingly, Bridger reaches a comparable level of sensitivity and accuracy with Cufflinks. Bridger is available at https://sourceforge.net/projects/rnaseqassembly/files/?source=navbar.

High-throughput RNA-seq technology has provided an unprecedented opportunity to reveal the very complex structures of transcriptomes. However, it is an important and highly challenging task to assemble vast amounts of short RNA-seq reads into transcriptomes with alternative splicing isoforms. In this study, we present a novel de novo assembler, BinPacker, by modeling the transcriptome assembly problem as tracking a set of trajectories of items with their sizes representing coverage of their corresponding isoforms by solving a series of bin-packing problems. This approach, which subtly integrates coverage information into the procedure, has two exclusive features: 1) only splicing junctions are involved in the assembling procedure; 2) massive pell-mell reads are assembled seemingly by moving a comb along junction edges on a splicing graph. Being tested on both real and simulated RNA-seq datasets, it outperforms almost all the existing de novo assemblers on all the tested datasets, and even outperforms those ab initio assemblers on the real dog dataset. In addition, it runs substantially faster and requires less memory space than most of the assemblers. BinPacker is published under GNU GENERAL PUBLIC LICENSE and the source is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_1.0.tar.gz/download. Quick installation version is available from: http://sourceforge.net/projects/transcriptomeassembly/files/BinPacker_binary.tar.gz/download. The availability of RNA-seq technology drives the development of algorithms for transcriptome assembly from very short RNA sequences. However, the problem of how to (de novo) assemble transcriptome using RNA-seq datasets has not been modeled well; e.g. sequence coverage information has even not been accurately and effectively integrated into the appropriate assembling procedure, leading to a bottleneck that all the existing (de novo) strategies have encountered. We present a novel approach to remodel the problem as tracking a set of trajectories of items with their sizes representing the coverage of their corresponding isoforms by solving a series of bin-packing problems. This approach, which subtly integrates the coverage information into the procedure, has two exclusive features: 1) only splicing junctions are involved in the assembling procedure; 2) massive pell-mell reads are assembled seemingly by moving a comb along junction edges on a splicing graph. Being tested on both real and simulated RNA-seq datasets, it outperforms almost all existing de novo assemblers on all the tested datasets, even outperforms those ab initio assemblers on the dog dataset, in terms of commonly used comparison standards.

Transcriptome assemblers aim to reconstruct full-length transcripts from RNA-seq data. We present TransComb, a genome-guided assembler developed based on a junction graph, weighted by a bin-packing strategy and paired-end information. A newly designed extension method based on weighted junction graphs can accurately extract paths representing expressed transcripts, whether they have low or high expression levels. Tested on both simulated and real datasets, TransComb demonstrates significant improvements in both recall and precision over leading assemblers, including StringTie, Cufflinks, Bayesembler, and Traph. In addition, it runs much faster and requires less memory on average. TransComb is available at http://sourceforge.net/projects/transcriptomeassembly/files/ .

Biclustering algorithms, which aim to provide an effective and efficient way to analyze gene expression data by finding a group of genes with trend-preserving expression patterns under certain conditions, have been widely developed since Morganet al.pioneered a work about partitioning a data matrix into submatrices with approximately constant values. However, the identification of general trend-preserving biclusters which are the most meaningful substructures hidden in gene expression data remains a highly challenging problem. We found an elementary method by which biologically meaningful trend-preserving biclusters can be readily identified from noisy and complex large data. The basic idea is to apply the longest common subsequence (LCS) framework to selected pairs of rows in an index matrix derived from an input data matrix to locate a seed for each bicluster to be identified. We tested it on synthetic and real datasets and compared its performance with currently competitive biclustering tools. We found that the new algorithm, named UniBic, outperformed all previous biclustering algorithms in terms of commonly used evaluation scenarios except for BicSPAM on narrow biclusters. The latter was somewhat better at finding narrow biclusters, the task for which it was specifically designed.

Identification of a few cancer driver mutation genes from a much larger number of passenger mutation genes in cancer samples remains a highly challenging task. Here, a novel method for distinguishing the driver genes from the passenger genes by effective integration of somatic mutation data and molecular interaction data using a maximal mutational impact function (MaxMIF) is presented. When evaluated on six somatic mutation datasets of Pan‐Cancer and 19 datasets of different cancer types from TCGA, MaxMIF almost always significantly outperforms all the existing state‐of‐the‐art methods in terms of predictive accuracy, sensitivity, and specificity. It recovers about 30% more known cancer genes in 500 top‐ranked candidate genes than the best among the other tools evaluated. MaxMIF is also highly robust to data perturbation. Intriguingly, MaxMIF is able to identify potential cancer driver genes, with strong experimental data support. Therefore, MaxMIF can be very useful for identifying or prioritizing cancer driver genes in the increasing number of available cancer genomic data.

We present TransLiG, a new de novo transcriptome assembler, which is able to integrate the sequence depth and pair-end information into the assembling procedure by phasing paths and iteratively constructing line graphs starting from splicing graphs. TransLiG is shown to be significantly superior to all the salient de novo assemblers in both accuracy and computing resources when tested on artificial and real RNA-seq data. TransLiG is freely available at https://sourceforge.net/projects/transcriptomeassembly/files/ .