Metaheuristics for Search Problems in Genomics - New Algorithms and Applications

In this thesis we made the first steps towards the systematic application of a methodology for automatically building formal models of complex biological systems. Such a methodology could be useful also to design artificial systems possessing desirable properties such as robustness and evolvability. The approach we follow in this thesis is to manipulate formal models by means of adaptive search methods called metaheuristics. In the first part of the thesis we develop state-of-the-art hybrid metaheuristic algorithms to tackle two important problems in genomics, namely, the Haplotype Inference by parsimony and the Founder Sequence Reconstruction Problem. We compare our algorithms with other effective techniques in the literature, we show strength and limitations of our approaches to various problem formulations and, finally, we propose further enhancements that could possibly improve the performance of our algorithms and widen their applicability. In the second part, we concentrate on Boolean network (BN) models of gene regulatory networks (GRNs). We detail our automatic design methodology and apply it to four use cases which correspond to different design criteria and address some limitations of GRN modeling by BNs. Finally, we tackle the Density Classification Problem with the aim of showing the learning capabilities of BNs. Experimental evaluation of this methodology shows its efficacy in producing network that meet our design criteria. Our results, coherently to what has been found in other works, also suggest that networks manipulated by a search process exhibit a mixture of characteristics typical of different dynamical regimes.

Formulations and Metaheuristics for combinatorial optimization problems

Combinatorial optimization problems have been strongly addressed throughout history. Their study involves highly applied problems that must be solved in reasonable times. This doctoral Thesis addresses three Operations Research problems: the first deals with the Traveling Salesman Problem with Pickups and Delivery with Handling cost, which was approached with two metaheuristics based on Iterated Local Search; the results show that the proposed methods are faster and obtain good results respect to the metaheuristics from the literature. The second problem corresponds to the Quadratic Multiple Knapsack Problem, and polynomial formulations and relaxations are presented for new instances of the problem; in addition, a metaheuristic and a matheuristic are proposed that are competitive with state of the art algorithms. Finally, an Open-Pit Mining problem is approached. This problem is solved with a parallel genetic algorithm that allows excavations using truncated cones. Each of these problems was computationally tested with difficult instances from the literature, obtaining good quality results in reasonable computational times, and making significant contributions to the state of the art techniques of Operations Research.