Conjunctive Bayesian networks

Conjunctive Bayesian networks (CBNs) are graphical models that describe the accumulation of events which are constrained in the order of their occurrence. A CBN is given by a partial order on a (finite) set of events. CBNs generalize the oncogenetic tree models of Desper et al. by allowing the occurrence of an event to depend on more than one predecessor event. The present paper studies the statistical and algebraic properties of CBNs. We determine the maximum likelihood parameters and present a combinatorial solution to the model selection problem. Our method performs well on two datasets where the events are HIV mutations associated with drug resistance. Concluding with a study of the algebraic properties of CBNs, we show that CBNs are toric varieties after a coordinate transformation and that their ideals possess a quadratic Gr\"{o}bner basis.Comment: Published in at http://dx.doi.org/10.3150/07-BEJ6133 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Systems approaches and algorithms for discovery of combinatorial therapies

Effective therapy of complex diseases requires control of highly non-linear complex networks that remain incompletely characterized. In particular, drug intervention can be seen as control of signaling in cellular networks. Identification of control parameters presents an extreme challenge due to the combinatorial explosion of control possibilities in combination therapy and to the incomplete knowledge of the systems biology of cells. In this review paper we describe the main current and proposed approaches to the design of combinatorial therapies, including the empirical methods used now by clinicians and alternative approaches suggested recently by several authors. New approaches for designing combinations arising from systems biology are described. We discuss in special detail the design of algorithms that identify optimal control parameters in cellular networks based on a quantitative characterization of control landscapes, maximizing utilization of incomplete knowledge of the state and structure of intracellular networks. The use of new technology for high-throughput measurements is key to these new approaches to combination therapy and essential for the characterization of control landscapes and implementation of the algorithms. Combinatorial optimization in medical therapy is also compared with the combinatorial optimization of engineering and materials science and similarities and differences are delineated.Comment: 25 page

Cheating for Problem Solving: A Genetic Algorithm with Social Interactions

We propose a variation of the standard genetic algorithm that incorporates social interaction between the individuals in the population. Our goal is to understand the evolutionary role of social systems and its possible application as a non-genetic new step in evolutionary algorithms. In biological populations, ie animals, even human beings and microorganisms, social interactions often affect the fitness of individuals. It is conceivable that the perturbation of the fitness via social interactions is an evolutionary strategy to avoid trapping into local optimum, thus avoiding a fast convergence of the population. We model the social interactions according to Game Theory. The population is, therefore, composed by cooperator and defector individuals whose interactions produce payoffs according to well known game models (prisoner's dilemma, chicken game, and others). Our results on Knapsack problems show, for some game models, a significant performance improvement as compared to a standard genetic algorithm.Comment: 7 pages, 5 Figures, 5 Tables, Proceedings of Genetic and Evolutionary Computation Conference (GECCO 2009), Montreal, Canad

Artificial and Natural Genetic Information Processing

Conventional methods of genetic engineering and more recent genome editing techniques focus on identifying genetic target sequences for manipulation. This is a result of historical concept of the gene which was also the main assumption of the ENCODE project designed to identify all functional elements in the human genome sequence. However, the theoretical core concept changed dramatically. The old concept of genetic sequences which can be assembled and manipulated like molecular bricks has problems in explaining the natural genome-editing competences of viruses and RNA consortia that are able to insert or delete, combine and recombine genetic sequences more precisely than random-like into cellular host organisms according to adaptational needs or even generate sequences de novo. Increasing knowledge about natural genome editing questions the traditional narrative of mutations (error replications) as essential for generating genetic diversity and genetic content arrangements in biological systems. This may have far-reaching consequences for our understanding of artificial genome editing

Data Science and Ebola

Data Science---Today, everybody and everything produces data. People produce large amounts of data in social networks and in commercial transactions. Medical, corporate, and government databases continue to grow. Sensors continue to get cheaper and are increasingly connected, creating an Internet of Things, and generating even more data. In every discipline, large, diverse, and rich data sets are emerging, from astrophysics, to the life sciences, to the behavioral sciences, to finance and commerce, to the humanities and to the arts. In every discipline people want to organize, analyze, optimize and understand their data to answer questions and to deepen insights. The science that is transforming this ocean of data into a sea of knowledge is called data science. This lecture will discuss how data science has changed the way in which one of the most visible challenges to public health is handled, the 2014 Ebola outbreak in West Africa.Comment: Inaugural lecture Leiden Universit