Polynomial supertree methods in phylogenomics: algorithms, simulations and software

One of the objectives in modern biology, especially phylogenetics, is to build larger clades of the Tree of Life. Large-scale phylogenetic analysis involves several serious challenges. The aim of this thesis is to contribute to some of the open problems in this context. In computational phylogenetics, supertree methods provide a way to reconstruct larger clades of the Tree of Life. We present a novel polynomial time approach for the computation of supertrees called FlipCut supertree. Our method combines the computation of minimum cuts from graph-based methods with a matrix representation method, namely Minimum Flip Supertrees. Here, the input trees are encoded in a 0/1/?-matrix. We present a heuristic to search for a minimum set of 0/1-flips such that the resulting matrix admits a directed perfect phylogeny. In contrast to other polynomial time approaches, our results can be interpreted in the sense that we try to minimize a global objective function, namely the number of flips in the input matrix. We extend our approach by using edge weights to weight the columns of the 0/1/?-matrix. In order to compare our new FlipCut supertree method with other recent polynomial supertree methods and matrix representation methods, we present a large scale simulation study using two different data sets. Our findings illustrate the trade-off between accuracy and running time in supertree construction, as well as the pros and cons of different supertree approaches. Furthermore, we present EPoS, a modular software framework for phylogenetic analysis and visualization. It fills the gap between command line-based algorithmic packages and visual tools without sufficient support for computational methods. By combining a powerful graphical user interface with a plugin system that allows simple integration of new algorithms, visualizations and data structures, we created a framework that is easy to use, to extend and that covers all important steps of a phylogenetic analysis

Fixed-parameter algorithms for some combinatorial problems in bioinformatics

Fixed-parameterized algorithmics has been developed in 1990s as an approach to solve NP-hard problem optimally in a guaranteed running time. It offers a new opportunity to solve NP-hard problems exactly even on large problem instances. In this thesis, we apply fixed-parameter algorithms to cope with three NP-hard problems in bioinformatics: Flip Consensus Tree Problem is a combinatorial problem arising in computational phylogenetics. Using the formulation of the Flip Consensus Tree Problem as a graph-modification problem, we present a set of data reduction rules and two fixed-parameter algorithms with respect to the number of modifications. Additionally, we discuss several heuristic improvements to accelerate the running time of our algorithms in practice. We also report computational results on phylogenetic data. Weighted Cluster Editing Problem is a graph-modification problem, that arises in computational biology when clustering objects with respect to a given similarity or distance measure. We present one of our fixed-parameter algorithms with respect to the minimum modification cost and describe the idea of our fastest algorithm for this problem and its unweighted counterpart. Bond Order Assignment Problem asks for a bond order assignment of a molecule graph that minimizes a penalty function. We prove several complexity results on this problem and give two exact fixed-parameter algorithms for the problem. Our algorithms base on the dynamic programming approach on a tree decomposition of the molecule graph. Our algorithms are fixed-parameter with respect to the treewidth of the molecule graph and the maximum atom valence. We implemented one of our algorithms with several heuristic improvements and evaluate our algorithm on a set of real molecule graphs. It turns out that our algorithm is very fast on this dataset and even outperforms a heuristic algorithm that is usually used in practice

Étude de la coopération hôte-microbiote par des problèmes d'optimisation basés sur la complétion de réseaux métaboliques

Systems biology relies on computational biology to integrate knowledge and data, for a better understanding of organisms’ physiology. Challenges reside in the applicability of methods and tools to non-model organisms, for instance in marine biology. Sequencing advances and the growing importance of elucidating microbiotas’ roles, have led to an increased interest into these organisms. This thesis focuses on the modeling of the metabolism through networks, and of its functionality using graphs and constraints semantics. In particular, a first part presents work on gap-filling metabolic networks in the context of non-model organisms. A graph-based method is benchmarked and validated and a hybrid one is developed using Answer Set Programming (ASP) and linear programming. Such gap-filling is applied on algae and extended to decipher putative interactions between Ectocarpus siliculosus and a symbiotic bacterium. In this direction, the second part of the thesis aims at proposing formalisms and implementation of a tool for selecting and screening communities of interest within microbiotas. It enables to scale to large microbiotas and, with a two-step approach, to suggest symbionts that fit the desired objective. The modeling supports the computation of exchanges, and solving can cover the whole solution space. Applications are presented on the human gut microbiota and the selection of bacterial communities for a brown alga. Altogether, this thesis proposes modeling, software and biological applications using graph-based semantics to support the elaboration of hypotheses for elucidating the metabolism of organisms.La biologie des systèmes intègre données et connaissances par des méthodes bioinformatiques, afin de mieux appréhender la physiologie des organismes. Une problématique est l’applicabilité de ces techniques aux organismes non modèles, au centre de plus en plus d’études, grâce aux avancées de séquençage et à l’intérêt croissant de la recherche sur les microbiotes. Cette thèse s’intéresse à la modélisation du métabolisme par des réseaux, et de sa fonctionnalité par diverses sémantiques basées sur les graphes et les contraintes stoechiométriques. Une première partie présente des travaux sur la complétion de réseaux métaboliques pour les organismes non modèles. Une méthode basée sur les graphes est validée, et une seconde, hybride, est développée, en programmation par ensembles réponses (ASP). Ces complétions sont appliquées à des réseaux métaboliques d’algues en biologie marine, et étendues à la recherche de complémentarité métabolique entre Ectocarpus siliculosus et une bactérie symbiotique. En s’appuyant sur les méthodes de complétion, la seconde partie de la thèse vise à proposer et implémenter une sélection de communautés à l’échelle de grands microbiotes. Une approche en deux étapes permet de suggérer des symbiotes pour l’optimisation d’un objectif donné. Elle supporte la modélisation des échanges et couvre tout l’espace des solutions. Des applications sur le microbiote intestinal humain et la sélection de bactéries pour une algue brune sont présentées. Dans l’ensemble, cette thèse propose de modéliser, développer et appliquer des méthodes reposant sur des sémantiques de graphe pour élaborer des hypothèses sur le métabolisme des organismes

LIPIcs, Volume 244, ESA 2022, Complete Volume

LIPIcs, Volume 244, ESA 2022, Complete Volum

Biologists, policymakers and other specimens: A story about collecting, regulating and social interactions

Abstract: This document is a story of the regulation of the practices of biology in Colombia. It unfolds, mainly, in the first decade of this millennium and it is constructed by exploring different specimens that inhabit quite different ecosystems in this sociotechnical controversy: News, videos, letters, conversations, scientific articles, forums and even fictional situations. This story of regulation of science has a “happy end”, or, a victory for the community of biologists when were published by Ministry of Environment the Decrees 1375 and 1376, in 2013, which regulate the practice of collecting biological specimens for scientific purposes and the biological collections. But before a process of policymaking was performed with a relevant participation of biologists, it was necessary to configure a problematic situation, full of associations which help scientists to mobilize the needed resources for promoting a change in the normativity that regulates their practices. While constructing this story, a constant parallelism between the “world of biology” and the process of doing research of communities of biologist is done, generating a thesis that does not only talk about a change in the regulatory framework of biology but about doing collecting and analysing work for the understanding of a scientific community.Resumen: Este documento es una historia de la regulación de las prácticas de la biología en Colombia. Se desarrolla, principalmente, en la primera década de este milenio y es construida mediante la exploración de diferentes especímenes que habitan diferentes ecosistemas en esta controversia sociotécnica: Noticias, videos, cartas, conversaciones, artículos científicos, foros e incluso situaciones ficticias. Esta historia de regulación de la ciencia tiene un “final feliz”, o, una victoria de la comunidad de biólogos cuando fueron publicados por el Ministerio de Ambiente y Desarrollo Sostenible los decretos 1375 y 1376, en el año 2013, los cuales regulan la práctica de colectar especímenes biológicos con fines científicos y las colecciones biológicas. Pero antes de que el proceso de creación de políticas fuera realizado con una participación relevante de biólogos, fue necesario configurar una situación problemática, llena de asociaciones las cuales ayudaron a los científicos a movilizar los recursos necesarios para promover un cambio en la normatividad que regula sus prácticas. Mientras se construía esta historia, se realizó un constante paralelismo entre el “mundo de la biología” y el proceso de hacer investigación sobre las comunidades de biólogos, generándose una tesis que no solamente habla sobre un cambio en el marco regulatorio de la biología sino también sobre hacer trabajo de colecta y análisis para entender una comunidad científica.Maestrí