Helsinki Institute for Information Technology

About: Helsinki Institute for Information Technology is a facility organization based out in Espoo, Finland. It is known for research contribution in the topics: Population & Bayesian network. The organization has 630 authors who have published 1962 publications receiving 63426 citations.

Multivariate multi-way analysis of multi-source data

Abstract: Motivation: Analysis of variance (ANOVA)-type methods are the default tool for the analysis of data with multiple covariates. These tools have been generalized to the multivariate analysis of high-throughput biological datasets, where the main challenge is the problem of small sample size and high dimensionality. However, the existing multi-way analysis methods are not designed for the currently increasingly important experiments where data is obtained from multiple sources. Common examples of such settings include integrated analysis of metabolic and gene expression profiles, or metabolic profiles from several tissues in our case, in a controlled multi-way experimental setup where disease status, medical treatment, gender and time-series are usual covariates. Results: We extend the applicability area of multivariate, multi-way ANOVA-type methods to multi-source cases by introducing a novel Bayesian model. The method is capable of finding covariate-related dependencies between the sources. It assumes the measurements consist of groups of similarly behaving variables, and estimates the multivariate covariate effects and their interaction effects for the discovered groups of variables. In particular, the method partitions the effects to those shared between the sources and to source-specific ones. The method is specifically designed for datasets with small sample sizes and high dimensionality. We apply the method to a lipidomics dataset from a lung cancer study with two-way experimental setup, where measurements from several tissues with mostly distinct lipids have been taken. The method is also directly applicable to gene expression and proteomics. Availability: An R-implementation is available at http://www.cis.hut.fi/projects/mi/software/multiWayCCA/ Contact:ilkka.huopaniemi@tkk.fi; samuel.kaski@tkk.fi

Dimensionality Reduction for Data Visualization [Applications Corner]

Abstract: Dimensionality reduction is one of the basic operations in the toolbox of data analysts and designers of machine learning and pattern recognition systems. Given a large set of measured variables but few observations, an obvious idea is to reduce the degrees of freedom in the measurements by rep resenting them with a smaller set of more "condensed" variables. Another reason for reducing the dimensionality is to reduce computational load in further processing. A third reason is visualization.

Kernelized Bayesian Matrix Factorization.

Abstract: We extend kernelized matrix factorization with a full-Bayesian treatment and with an ability to work with multiple side information sources expressed as different kernels. Kernels have been introduced to integrate side information about the rows and columns, which is necessary for making out-of-matrix predictions. We discuss specifically binary output matrices but extensions to realvalued matrices are straightforward. We extend the state of the art in two key aspects: (i) A full-conjugate probabilistic formulation of the kernelized matrix factorization enables an efficient variational approximation, whereas full-Bayesian treatments are not computationally feasible in the earlier approaches. (ii) Multiple side information sources are included, treated as different kernels in multiple kernel learning which additionally reveals which side sources are informative. We then show that the framework can also be used for supervised and semi-supervised multilabel classification and multi-output regression, by considering samples and outputs as the domains where matrix factorization operates. Our method outperforms alternatives in predicting drug-protein interactions on two data sets. On multilabel classification, our algorithm obtains the lowest Hamming losses on 10 out of 14 data sets compared to five state-of-the-art multilabel classification algorithms. We finally show that the proposed approach outperforms alternatives in multi-output regression experiments on a yeast cell cycle data set.

Circumspect descent prevails in solving random constraint satisfaction problems

Abstract: We study the performance of stochastic local search algorithms for random instances of the K-satisfiability (K-SAT) problem. We present a stochastic local search algorithm, ChainSAT, which moves in the energy landscape of a problem instance by never going upwards in energy. ChainSAT is a focused algorithm in the sense that it focuses on variables occurring in unsatisfied clauses. We show by extensive numerical investigations that ChainSAT and other focused algorithms solve large K-SAT instances almost surely in linear time, up to high clause-to-variable ratios α; for example, for K = 4 we observe linear-time performance well beyond the recently postulated clustering and condensation transitions in the solution space. The performance of ChainSAT is a surprise given that by design the algorithm gets trapped into the first local energy minimum it encounters, yet no such minima are encountered. We also study the geometry of the solution space as accessed by stochastic local search algorithms.

Global proteomics profiling improves drug sensitivity prediction: results from a multi-omics, pan-cancer modeling approach.

Abstract: Motivation Proteomics profiling is increasingly being used for molecular stratification of cancer patients and cell-line panels. However, systematic assessment of the predictive power of large-scale proteomic technologies across various drug classes and cancer types is currently lacking. To that end, we carried out the first pan-cancer, multi-omics comparative analysis of the relative performance of two proteomic technologies, targeted reverse phase protein array (RPPA) and global mass spectrometry (MS), in terms of their accuracy for predicting the sensitivity of cancer cells to both cytotoxic chemotherapeutics and molecularly targeted anticancer compounds. Results Our results in two cell-line panels demonstrate how MS profiling improves drug response predictions beyond that of the RPPA or the other omics profiles when used alone. However, frequent missing MS data values complicate its use in predictive modeling and required additional filtering, such as focusing on completely measured or known oncoproteins, to obtain maximal predictive performance. Rather strikingly, the two proteomics profiles provided complementary predictive signal both for the cytotoxic and targeted compounds. Further, information about the cellular-abundance of primary target proteins was found critical for predicting the response of targeted compounds, although the non-target features also contributed significantly to the predictive power. The clinical relevance of the selected protein markers was confirmed in cancer patient data. These results provide novel insights into the relative performance and optimal use of the widely applied proteomic technologies, MS and RPPA, which should prove useful in translational applications, such as defining the best combination of omics technologies and marker panels for understanding and predicting drug sensitivities in cancer patients. Availability and implementation Processed datasets, R as well as Matlab implementations of the methods are available at https://github.com/mehr-een/bemkl-rbps. Contact mehreen.ali@helsinki.fi or tero.aittokallio@fimm.fi. Supplementary information Supplementary data are available at Bioinformatics online.