Finding undetected protein associations in cell signaling by belief propagation

External information propagates in the cell mainly through signaling cascades and transcriptional activation, allowing it to react to a wide spectrum of environmental changes. High throughput experiments identify numerous molecular components of such cascades that may, however, interact through unknown partners. Some of them may be detected using data coming from the integration of a protein-protein interaction network and mRNA expression profiles. This inference problem can be mapped onto the problem of finding appropriate optimal connected subgraphs of a network defined by these datasets. The optimization procedure turns out to be computationally intractable in general. Here we present a new distributed algorithm for this task, inspired from statistical physics, and apply this scheme to alpha factor and drug perturbations data in yeast. We identify the role of the COS8 protein, a member of a gene family of previously unknown function, and validate the results by genetic experiments. The algorithm we present is specially suited for very large datasets, can run in parallel, and can be adapted to other problems in systems biology. On renowned benchmarks it outperforms other algorithms in the field.Comment: 6 pages, 3 figures, 1 table, Supporting Informatio

Cavity algorithms under global constraints: classical and quantum problems

The starting point of my thesis work was the study of optimization algorithms based on cavity method. These algorithms have been developed to a high degree of complexity in the last decade and they are also known as message passing algorithms (MPAs). My work has started by a question posed by my supervisor: what links can be found between those different approaches to the same problems? The starting aim of the PhD project was to explore the new ideas and algorithms that could result from a cross-fertilization between different approaches. During the first years we made a long and accurate comparison between different algorithms on a specific COP: the prize collecting Steiner tree problem. Looking to MPAs as an evolution of probability distributions of discrete variables led me to find some possible links with many body quantum physics, where typically we deal with probability amplitudes over discrete variables. In the recent years several results have appeared concerning the extension of the cavity method and message passing technics to quantum context. In 2012 Ramezanpour proposed a method, the variational quantum cavity method (VQCM), for finding approximate ground state wave functions based on a new messages passing algorithm used in stochastic optimization. Ramezanpour and I have extended this approach to find low excited states. In the last year of my Ph.D. I simplify the VQCM using imaginary time evolution operator. Moreover I extend this approach to find finite temperature density matri

Computational Methods in Systems Biology, 7th International Conference, CMSB 2009

none2siThe proceedings contain 21 papers. The topics discussed include: modelling biological clocks with bio-PEPA: stochasticity and robustness for the neurospora crassa circadian network; quantitative pathway logic for computational biology; a prize-collecting steiner tree approach for transduction network inference; formal analysis of the genetic toggle; control strategies for the regulation of the eukaryotic heat shock response; computing reachable states for nonlinear biological models; on coupling models using model-checking: effects of irinotecan injections on the mammalian cell cycle; approximation of event probabilities in noisy cellular processes; equivalence and discretisation in bio-PEPA; improved parameter estimation for completely observed ordinary differential equations with application to biological systems; a Bayesian approach to model checking biological systems; probabilistic approximations of signaling pathway dynamics; and a reduction of logical regulatory graphs preserving essential dynamical properties.noneP. Degano; R. GorrieriP. Degano; R. Gorrier