{"id":35,"date":"2013-10-04T15:47:08","date_gmt":"2013-10-04T18:47:08","guid":{"rendered":"http:\/\/eventos.cmm.uchile.cl\/bioasp\/?page_id=35"},"modified":"2013-10-04T16:11:00","modified_gmt":"2013-10-04T19:11:00","slug":"contenidos","status":"publish","type":"page","link":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/contenidos\/","title":{"rendered":"Contenidos"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-42 alignright\" alt=\"bioinfo\" src=\"http:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-content\/uploads\/sites\/6\/2013\/10\/bioinfo-123x300.png\" width=\"150\" height=\"366\" \/><\/p>\n<p style=\"text-align: left\" align=\"CENTER\">Summary<\/p>\n<p style=\"text-align: left\" align=\"CENTER\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\"><span style=\"line-height: 1.5\">Systems biology is an emerging field aiming at the investigation and understanding of biology at a system and multi-scale level. After biological entities have been identified in a specific environment, it remains to elucidate how they interact with each other in order to carry out a particular biological function. Therefore the construction of mathematical and predictive models is a fundamental goal of this field. In this context, regulatory, metabolic and signaling networks are crucial for the understanding of complex biological systems. Importantly, they are involved in bio-medical, bio-energy, bio-mining and agriculture processes. Hence, their control has a crucial impact on drug target identification, diagnosis, cancer research, bio-fuels and drought tolerance among other applications. During the last decade, many efforts have been made to develop relevant formalisms and modeling frameworks to take into account the specificities of such biological systems. In the lack of quantitative details, qualitative approaches based on graph theory or (Boolean) logical networks have become very popular.<\/span><\/span><\/span><\/p>\n<p align=\"JUSTIFY\">\n<p align=\"JUSTIFY\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Nowadays, some major challenges related to the identification, control and pruning of biological networks remain open. Further, dealing with uncertainty and its consequences is a fundamental issue on systems biology, and particularly in the context of qualitative modeling approaches. In general, due to factors including experimental error, limitations in the amount of data available, incompleteness of our prior knowledge, and inherent mathematical properties of the models, there are multiple \u201cright\u201d answers to the same question. Hence, how to turn a possibly very large number of answers into valuable insights for biologists is a fundamental and critical aspect on this subject.<\/span><\/span><\/p>\n<p align=\"JUSTIFY\"><a name=\"_GoBack\"><\/a> <span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">In this course we will investigate these issues from the point of view of Knowledge Representation and Reasoning, and more specifically Answer Set Programming (ASP). ASP is a declarative problem-solving paradigm in which a problem is encoded as a set of logic rules such that its models (answer sets) represent solutions to the problem. In general, ASP can be used to solve hard combinatoria<\/span><\/span><\/p>\n<p align=\"JUSTIFY\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">l search and optimization problems. The distinct features of ASP are its rich yet simple modeling language and the highly efficient solvers publicly available. Further, modern ASP solvers support several reasoning modes for assessing the multi<\/span><\/span><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">tude of solutions, among them, regular and projective enumeration, intersection, union, and multi-criteria optimization. Therefore, after a decade of research and development, ASP is a very attractive computational approach to answer relevant questions arising in systems biology as the ones described above. In fact, some of these questions have been successfully addressed with ASP in various settings over the last few years. However, it remains to be elucidated whether ASP technology is mature enough to cope with real-life problem instances, and more importantly, bring new insights for biologists.<\/span><\/span><\/p>\n<p align=\"JUSTIFY\"><span style=\"font-family: Arial, serif\"><span><b>Contents<\/b><\/span><\/span><\/p>\n<p><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Motivation (2h)<\/span><\/span><\/span><\/p>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Bioinformatics \/ Systems Biology \/ Synthetic Biology<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Bioinformatics: aims at understanding the isolated parts<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Systems Biology: aims at understanding the systems<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Synthetic Biology: aims at designing the systems<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Large amount of heterogeneous and noisy experimental data:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Transcriptomics<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Metabolomics<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Proteomics<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Large multi-scale biological systems<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Regulatory networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Metabolic networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Signaling networks<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Experiments are time consuming and expensive<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Gene expression<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Metabolites profiles<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Phosphorylation activity<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Applications<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Medicine: cancer, vaccines, drug discovery<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Energy: bio-diesel, bio-ethanol<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Agriculture: drought tolerance<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Mining: bioleaching copper<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Approach<\/span><\/span><\/span>\n<ul>\n<li><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Reasoning over a complete family of feasible models instead of selecting one model<\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Identify robust information from the family of models which deserves a detailed dynamical study<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Knowledge Representation and Reasoning in Systems Biology (1h)<\/span><\/span><\/span><\/p>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Knowledge<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Incomplete<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Contradictory<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Incorrect<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Vague<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Representation<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Biological networks:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">(un)signed and (un)directed graphs<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Qualitative relations\/interactions: activates, inhibits, regulates, co-expressed, produces, consumes<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Data discretization<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Boolean: present\/absent; up\/down; active\/inactive<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">(un) signed: {-1, 0, 1}<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Linear: integer interval, e.g. [0,100]<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Logarithmic: several levels, e.g. {0, 10, 100, 1000}<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Reasoning<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">(in) consistency detection (Diagnosis &amp; Repairing)<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Models refinement \/ inference (Combinatorial optimization)<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Robust predictions<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Hypothesis generation<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Experimental design<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Answer Set Programming (1h)<\/span><\/span><\/span><\/p>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Logic Programming &#8211; AI &#8211; KRR<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">General purpose problem solving paradigm \u00a0<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Fully declarative<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Highly expressive<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">High performance dedicated solvers<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Deduction, Abduction and Induction<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Defaults (closed-world assumption) and recursive definitions<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Applications: Robotics, Scheduling, Planning, Diagnosis, Configuration, \u2026<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Related methods:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">SAT: Boolean Satisfiability<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">ILP: Integer Linear Programming<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">CP: Constraint Programming<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">CLP(FD): Constraint Logic Programming over Finite Domains<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">ASP in a nutshell (3h):<\/span><\/span><\/span><\/p>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Workflows: declarative versus imperative programming<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Modeling methodology: Guess &amp; Check (NP problems)<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Basic syntax and semantics<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">The language gringo<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Basic rules<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Choice rules<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Integrity constraints<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Optimization<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">The solver clasp:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Basic usage<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Common options<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Configurations<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Reasoning modes<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Examples:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Graph coloring<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">N queens<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Travel Salesman Problem<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Potsdam Answer Set Solving Collection:<\/span><\/span><\/span>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">gringo<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">clasp<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">hclasp<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">unclasp<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">clingo<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">iclingo<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">clingcon<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">claspD<\/span><\/span><\/span><\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">ASP for Systems Biology: problems description and their ASP encodings (3h)<\/span><\/span><\/span><\/p>\n<ul>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Sign consistency detection in regulatory networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Learning Boolean logic models of signaling networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Intervention strategies in logic models of signaling networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Metabolic network completion<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">Precursor sets in metabolic networks<\/span><\/span><\/span><\/li>\n<li><span style=\"color: #000000\"><span style=\"font-family: Arial, serif\"><span style=\"font-size: small\">The BioASP python environment<\/span><\/span><\/span><\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Summary Systems biology is an emerging field aiming at the investigation and understanding of biology at a system and multi-scale level. After biological entities have been identified in a specific environment, it remains to elucidate how they interact with each other in order to carry out a particular biological function. Therefore the construction of mathematical &hellip; <a href=\"https:\/\/eventos.cmm.uchile.cl\/bioasp\/contenidos\/\" class=\"more-link\">Seguir leyendo <span class=\"screen-reader-text\">Contenidos<\/span> <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":6,"featured_media":0,"parent":0,"menu_order":3,"comment_status":"closed","ping_status":"closed","template":"","meta":{"inline_featured_image":false,"footnotes":""},"class_list":["post-35","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/pages\/35","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/comments?post=35"}],"version-history":[{"count":5,"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/pages\/35\/revisions"}],"predecessor-version":[{"id":44,"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/pages\/35\/revisions\/44"}],"wp:attachment":[{"href":"https:\/\/eventos.cmm.uchile.cl\/bioasp\/wp-json\/wp\/v2\/media?parent=35"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}