UNIVERSITE PARIS - SUD Ecole

Complex organization is found in many biological systems. For example, biopolymers could possess very hierarchic structure, which provides their functional peculiarity. Understating such complex organization allows to describe biological phenomena and predict molecule functions. Besides, we can try to characterize the specific phenomenon by some probabilistic quantities (variances, means, etc), assuming the primary biopolymer structure to be randomly formed according to some statistical distribution. Such a formulation is oriented toward evolutionary problems. Artificially constructed biological network is another common object of statistical physics with rich functional properties. A behavior of cells is a consequence of complex interactions between its numerous components, such as DNA, RNA, proteins and small molecules. Cells use signaling pathways and regulatory mechanisms to coordinate multiple processes, allowing them to respond and to adapt to changing environment. Recent theoretical advances allow us to describe cellular network structure using graph concepts to reveal the principal organizational features shared with numerous non-biological networks. The aim of this thesis is to develop bunch of methods for studying statistical and dynamic objects of complex architecture and, in particular, scale-free structures which have no characteristic spatial and/or time scale. For such systems the use of standard mathematical methods relying on the average behavior of the whole system, is often incorrect or useless, while a detailed many-body description is almost hopeless because of the combinatorial complexity of the problem. Here we focus on two problems. The first part address to the statistical analysis of random biopolymers. Apart from the evolutionary context, our studies cover more general problems of planar topology appeared in description of various systems, ranging from gauge theory i te l-0 09 19 60 6, v er si on 1 17 D ec 2 01 3 to biophysics. We investigate analytically and numerically a phase transition of a generic planar matching problem, from the regime where almost all the vertices are paired, to the situation where a finite fraction of them remains unmatched. In the second part of this work focus on statistical properties of networks. We demonstrate the possibility to define co-expression gene clusters within a network context from their specific motif distribution signatures. We also show how a method based on the shortest path function (SPF) can be applied to gene interactions sub-networks of co-expression gene clusters, to efficiently predict novel regulatory transcription factors (TFs). The biological significance of this method by applying it on groups of genes with a shared regulatory locus found by genomics is presented. Finally, we discuss formation of stable patters of motifs in networks under selective evolution in context of creation of islands of ”superfamilies”. ii te l-0 09 19 60 6, v er si on 1 17 D ec 2 01 3