Computational Biology

Computational biology is an interdisciplinary field that applies the techniques of computer science, applied mathematics, and statistics to address biological questions. OR is also interdisciplinary and applies the same mathematical and computational sciences, but to decision-making problems. Both focus on developing mathematical models and designing algorithms to solve them. Models in computational biology vary in their biological domain and can range from the interactions of genes and proteins to the relationships among organisms and species

Causality, Information and Biological Computation: An algorithmic software approach to life, disease and the immune system

Biology has taken strong steps towards becoming a computer science aiming at reprogramming nature after the realisation that nature herself has reprogrammed organisms by harnessing the power of natural selection and the digital prescriptive nature of replicating DNA. Here we further unpack ideas related to computability, algorithmic information theory and software engineering, in the context of the extent to which biology can be (re)programmed, and with how we may go about doing so in a more systematic way with all the tools and concepts offered by theoretical computer science in a translation exercise from computing to molecular biology and back. These concepts provide a means to a hierarchical organization thereby blurring previously clear-cut lines between concepts like matter and life, or between tumour types that are otherwise taken as different and may not have however a different cause. This does not diminish the properties of life or make its components and functions less interesting. On the contrary, this approach makes for a more encompassing and integrated view of nature, one that subsumes observer and observed within the same system, and can generate new perspectives and tools with which to view complex diseases like cancer, approaching them afresh from a software-engineering viewpoint that casts evolution in the role of programmer, cells as computing machines, DNA and genes as instructions and computer programs, viruses as hacking devices, the immune system as a software debugging tool, and diseases as an information-theoretic battlefield where all these forces deploy. We show how information theory and algorithmic programming may explain fundamental mechanisms of life and death.Comment: 30 pages, 8 figures. Invited chapter contribution to Information and Causality: From Matter to Life. Sara I. Walker, Paul C.W. Davies and George Ellis (eds.), Cambridge University Pres

Dagstuhl Reports : Volume 1, Issue 2, February 2011

Online Privacy: Towards Informational Self-Determination on the Internet (Dagstuhl Perspectives Workshop 11061) : Simone Fischer-Hübner, Chris Hoofnagle, Kai Rannenberg, Michael Waidner, Ioannis Krontiris and Michael Marhöfer Self-Repairing Programs (Dagstuhl Seminar 11062) : Mauro Pezzé, Martin C. Rinard, Westley Weimer and Andreas Zeller Theory and Applications of Graph Searching Problems (Dagstuhl Seminar 11071) : Fedor V. Fomin, Pierre Fraigniaud, Stephan Kreutzer and Dimitrios M. Thilikos Combinatorial and Algorithmic Aspects of Sequence Processing (Dagstuhl Seminar 11081) : Maxime Crochemore, Lila Kari, Mehryar Mohri and Dirk Nowotka Packing and Scheduling Algorithms for Information and Communication Services (Dagstuhl Seminar 11091) Klaus Jansen, Claire Mathieu, Hadas Shachnai and Neal E. Youn

Protein Sequence Alignment Analysis by Local Covariation: Coevolution Statistics Detect Benchmark Alignment Errors

The use of sequence alignments to understand protein families is ubiquitous in molecular biology. High quality alignments are difficult to build and protein alignment remains one of the largest open problems in computational biology. Misalignments can lead to inferential errors about protein structure, folding, function, phylogeny, and residue importance. Identifying alignment errors is difficult because alignments are built and validated on the same primary criteria: sequence conservation. Local covariation identifies systematic misalignments and is independent of conservation. We demonstrate an alignment curation tool, LoCo, that integrates local covariation scores with the Jalview alignment editor. Using LoCo, we illustrate how local covariation is capable of identifying alignment errors due to the reduction of positional independence in the region of misalignment. We highlight three alignments from the benchmark database, BAliBASE 3, that contain regions of high local covariation, and investigate the causes to illustrate these types of scenarios. Two alignments contain sequential and structural shifts that cause elevated local covariation. Realignment of these misaligned segments reduces local covariation; these alternative alignments are supported with structural evidence. We also show that local covariation identifies active site residues in a validated alignment of paralogous structures. Loco is available at https://sourceforge.net/projects/locoprotein/files

On the Origin of Biomolecular Networks

Biomolecular networks have already found great utility in characterizing complex biological systems arising from pairwise interactions amongst biomolecules. Here, we explore the important and hitherto neglected role of information asymmetry in the genesis and evolution of such pairwise biomolecular interactions. Information asymmetry between sender and receiver genes is identified as a key feature distinguishing early biochemical reactions from abiotic chemistry, and a driver of network topology as biomolecular systems become more complex. In this context, we review how graph theoretical approaches can be applied not only for a better understanding of various proximate (mechanistic) relations, but also, ultimate (evolutionary) structures encoded in such networks from among all types of variations they induce. Among many possible variations, we emphasize particularly the essential role of gene duplication in terms of signaling game theory, whereby sender and receiver gene players accrue benefit from gene duplication, leading to a preferential attachment mode of network growth. The study of the resulting dynamics suggests many mathematical/computational problems, the majority of which are intractable yet yield to efficient approximation algorithms, when studied through an algebraic graph theoretic lens. We relegate for future work the role of other possible generalizations, additionally involving horizontal gene transfer, sexual recombination, endo-symbiosis, etc., which enrich the underlying graph theory even further

Graph Theory and Networks in Biology

In this paper, we present a survey of the use of graph theoretical techniques in Biology. In particular, we discuss recent work on identifying and modelling the structure of bio-molecular networks, as well as the application of centrality measures to interaction networks and research on the hierarchical structure of such networks and network motifs. Work on the link between structural network properties and dynamics is also described, with emphasis on synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape