MOTIVATION: It is more and more common to perform multi-omics analyses to explore the genome at diverse levels and not only at a single level. Through integrative statistical methods, multi-omics data have the power to reveal new biological processes, potential biomarkers and subgroups in a cohort. Matrix factorization (MF) is an unsupervised statistical method that allows a clustering of individuals, but also reveals relevant omics variables from the various blocks. RESULTS: Here, we present PIntMF (Penalized Integrative Matrix Factorization), an MF model with sparsity, positivity and equality constraints. To induce sparsity in the model, we used a classical Lasso penalization on variable and individual matrices. For the matrix of samples, sparsity helps in the clustering, while normalization (matching an equality constraint) of inferred coefficients is added to improve interpretation. Moreover, we added an automatic tuning of the sparsity parameters using the famous glmnet package. We also proposed three criteria to help the user to choose the number of latent variables. PIntMF was compared with other state-of-the-art integrative methods including feature selection techniques in both synthetic and real data. PIntMF succeeds in finding relevant clusters as well as variables in two types of simulated data (correlated and uncorrelated). Next, PIntMF was applied to two real datasets (Diet and cancer), and it revealed interpretable clusters linked to available clinical data. Our method outperforms the existing ones on two criteria (clustering and variable selection). We show that PIntMF is an easy, fast and powerful tool to extract patterns and cluster samples from multi-omics data. AVAILABILITY AND IMPLEMENTATION: An R package is available at https://github.com/mpierrejean/pintmf. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Recent advances in NGS sequencing, microarrays and mass spectrometry for omics data production have enabled the generation and collection of different modalities of high-dimensional molecular data. The integration of multiple omics datasets is a statistical challenge, due to the limited number of individuals, the high number of variables and the heterogeneity of the datasets to integrate. Recently, a lot of tools have been developed to solve the problem of integrating omics data including canonical correlation analysis, matrix factorization and SM. These commonly used techniques aim to analyze simultaneously two or more types of omics. In this article, we compare a panel of 13 unsupervised methods based on these different approaches to integrate various types of multi-omics datasets: iClusterPlus, regularized generalized canonical correlation analysis, sparse generalized canonical correlation analysis, multiple co-inertia analysis (MCIA), integrative-NMF (intNMF), SNF, MoCluster, mixKernel, CIMLR, LRAcluster, ConsensusClustering, PINSPlus and multi-omics factor analysis (MOFA). We evaluate the ability of the methods to recover the subgroups and the variables that drive the clustering on eight benchmarks of simulation. MOFA does not provide any results on these benchmarks. For clustering, SNF, MoCluster, CIMLR, LRAcluster, ConsensusClustering and intNMF provide the best results. For variable selection, MoCluster outperforms the others. However, the performance of the methods seems to depend on the heterogeneity of the datasets (especially for MCIA, intNMF and iClusterPlus). Finally, we apply the methods on three real studies with heterogeneous data and various phenotypes. We conclude that MoCluster is the best method to analyze these omics data. Availability: An R package named CrIMMix is available on GitHub at https://github.com/CNRGH/crimmix to reproduce all the results of this article.

A number of bioinformatic or biostatistical methods are available for analyzing DNA copy number profiles measured from microarray or sequencing technologies. In the absence of rich enough gold standard data sets, the performance of these methods is generally assessed using unrealistic simulation studies, or based on small real data analyses. To make an objective and reproducible performance assessment, we have designed and implemented a framework to generate realistic DNA copy number profiles of cancer samples with known truth. These profiles are generated by resampling publicly available SNP microarray data from genomic regions with known copy-number state. The original data have been extracted from dilutions series of tumor cell lines with matched blood samples at several concentrations. Therefore, the signal-to-noise ratio of the generated profiles can be controlled through the (known) percentage of tumor cells in the sample. This article describes this framework and its application to a comparison study between methods for segmenting DNA copy number profiles from SNP microarrays. This study indicates that no single method is uniformly better than all others. It also helps identifying pros and cons of the compared methods as a function of biologically informative parameters, such as the fraction of tumor cells in the sample and the proportion of heterozygous markers. This comparison study may be reproduced using the open source and cross-platform R package jointseg, which implements the proposed data generation and evaluation framework: http://r-forge.r-project.org/R/?group_id=1562.