SUMMARY: For the analysis of high-throughput genomic data produced by next-generation sequencing (NGS) technologies, researchers need to identify linkage disequilibrium (LD) structure in the genome. In this work, we developed an R package gpart which provides clustering algorithms to define LD blocks or analysis units consisting of SNPs. The visualization tool in gpart can display the LD structure and gene positions for up to 20 000 SNPs in one image. The gpart functions facilitate construction of LD blocks and SNP partitions for vast amounts of genome sequencing data within reasonable time and memory limits in personal computing environments. AVAILABILITY AND IMPLEMENTATION: The R package is available at https://bioconductor.org/packages/gpart. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Motivation: Linkage disequilibrium (LD) block construction is required for research in population genetics and genetic epidemiology, including specification of sets of single nucleotide polymorphisms (SNPs) for analysis of multi-SNP based association and identification of haplotype blocks in high density sequencing data. Existing methods based on a narrow sense definition do not allow intermediate regions of low LD between strongly associated SNP pairs and tend to split high density SNP data into small blocks having high between-block correlation. Results: We present Big-LD, a block partition method based on interval graph modeling of LD bins which are clusters of strong pairwise LD SNPs, not necessarily physically consecutive. Big-LD uses an agglomerative approach that starts by identifying small communities of SNPs, i.e. the SNPs in each LD bin region, and proceeds by merging these communities. We determine the number of blocks using a method to find maximum-weight independent set. Big-LD produces larger LD blocks compared to existing methods such as MATILDE, Haploview, MIG ++, or S-MIG ++ and the LD blocks better agree with recombination hotspot locations determined by sperm-typing experiments. The observed average runtime of Big-LD for 13 288 240 non-monomorphic SNPs from 1000 Genomes Project autosome data (286 East Asians) is about 5.83 h, which is a significant improvement over the existing methods. Availability and implementation: Source code and documentation are available for download at http://github.com/sunnyeesl/BigLD. Contact: [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

BACKGROUND: Molecular predictor is a new tool for disease diagnosis, which uses gene expression to classify diagnostic category of a patient. The statistical challenge for constructing such a predictor is that there are thousands of genes to predict for the disease categories, but only a small number of samples are available. RESULTS: We proposed a gene network modular-based linear discriminant analysis approach by integrating 'essential' correlation structure among genes into the predictor in order that the modules or cluster structures of genes, which are related to the diagnostic classes we look for, can have potential biological interpretation. We evaluated performance of the new method with other established classification methods using three real data sets. CONCLUSIONS: Our results show that the new approach has the advantage of computational simplicity and efficiency with relatively lower classification error rates than the compared methods in many cases. The modular-based linear discriminant analysis approach induced in the study has the potential to increase the power of discriminant analysis for which sample sizes are small and there are large number of genes in the microarray studies.

MOTIVATION: Efficient and accurate ascertainment of copy number variations (CNVs) at the population level is essential to understand the evolutionary process and population genetics, and to apply CNVs in population-based genome-wide association studies for complex human diseases. We propose a novel Bayesian segmentation approach to identify CNVs in a defined population of any size. It is computationally efficient and provides statistical evidence for the detected CNVs through the Bayes factor. This approach has the unique feature of carrying out segmentation and assigning copy number status simultaneously-a desirable property that current segmentation methods do not share. RESULTS: In comparisons with popular two-step segmentation methods for a single individual using benchmark simulation studies, we find the new approach to perform competitively with respect to false discovery rate and sensitivity in breakpoint detection. In a simulation study of multiple samples with recurrent copy numbers, the new approach outperforms two leading single sample methods. We further demonstrate the effectiveness of our approach in population-level analysis of previously published HapMap data. We also apply our approach in studying population genetics of CNVs. AVAILABILITY: R programs are available at http://www.mshri.on.ca/mitacs/software/SOFTWARE.HTML

MOTIVATION: We developed an EM-random forest (EMRF) for Haseman-Elston quantitative trait linkage analysis that accounts for marker ambiguity and weighs each sib-pair according to the posterior identical by descent (IBD) distribution. The usual random forest (RF) variable importance (VI) index used to rank markers for variable selection is not optimal when applied to linkage data because of correlation between markers. We define new VI indices that borrow information from linked markers using the correlation structure inherent in IBD linkage data. RESULTS: Using simulations, we find that the new VI indices in EMRF performed better than the original RF VI index and performed similarly or better than EM-Haseman-Elston regression LOD score for various genetic models. Moreover, tree size and markers subset size evaluated at each node are important considerations in RFs. AVAILABILITY: The source code for EMRF written in C is available at www.infornomics.utoronto.ca/downloads/EMRF.