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Book
Computational Biology
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Year: 2019 Publisher: Australia Exon Publications

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Our understanding of biology has undergone a revolution in the past 20 years, driven by our ability to capture, store, interrogate and analyze the ever-increasing volumes of ‘omics’ data. Computational Biology, an integrated approach employing high performance computers, state-of-the art software and algorithms, mathematical modeling and statistical analyses have enabled us to unravel the seemingly impenetrable complexity of biological systems. This book draws together many of the latest cutting-edge developments in the field of Computational Biology. Each chapter draws on the expertise of leading researchers in the field to highlight the utility of specific technologies. The breadth of the text is impressive - from integrative biology in human diseases through the various branches of epigenomics, metabolomics and proteomics to biological sequencing and deep learning. Computational biology approaches for image-based analysis of multicellular spheroids, feature selection using entropy and cellular cryo-electron tomography structural pattern mining are covered. In addition, the key role of statistics in the analysis of high-dimensional multiset omics data and RNA sequencing are discussed in dedicated chapters. This book would have broad appeal to anyone with an interest in cutting edge computational biology.


Book
Elements of dynamic and 2-SAT programming : paths, trees, and cuts
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Year: 2021 Publisher: Berlin : Universitätsverlag der Technischen Universität Berlin,

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This thesis presents faster (in terms of worst-case running times) exact algorithms for special cases of graph problems through dynamic programming and 2-SAT programming. Dynamic programming describes the procedure of breaking down a problem recursively into overlapping subproblems, that is, subproblems with common subsubproblems. Given optimal solutions to these subproblems, the dynamic program then combines them into an optimal solution for the original problem. 2-SAT programming refers to the procedure of reducing a problem to a set of 2-SAT formulas, that is, boolean formulas in conjunctive normal form in which each clause contains at most two literals. Computing whether such a formula is satisfiable (and computing a satisfying truth assignment, if one exists) takes linear time in the formula length. Hence, when satisfying truth assignments to some 2-SAT formulas correspond to a solution of the original problem and all formulas can be computed efficiently, that is, in polynomial time in the input size of the original problem, then the original problem can be solved in polynomial time. We next describe our main results. Diameter asks for the maximal distance between any two vertices in a given undirected graph. It is arguably among the most fundamental graph parameters. We provide both positive and negative parameterized results for distance-from-triviality-type parameters and parameter combinations that were observed to be small in real-world applications. In Length-Bounded Cut, we search for a bounded-size set of edges that intersects all paths between two given vertices of at most some given length. We confirm a conjecture from the literature by providing a polynomial-time algorithm for proper interval graphs which is based on dynamic programming. k-Disjoint Shortest Paths is the problem of finding (vertex-)disjoint paths between given vertex terminals such that each of these paths is a shortest path between the respective terminals. Its complexity for constant k > 2 has been an open problem for over 20 years. Using dynamic programming, we show that k-Disjoint Shortest Paths can be solved in polynomial time for each constant k. The problem Tree Containment asks whether a phylogenetic tree T is contained in a phylogenetic network N. A phylogenetic network (or tree) is a leaf-labeled single-source directed acyclic graph (or tree) in which each vertex has in-degree at most one or out-degree at most one. The problem stems from computational biology in the context of the tree of life (the history of speciation). We introduce a particular variant that resembles certain types of uncertainty in the input. We show that if each leaf label occurs at most twice in a phylogenetic tree N, then the problem can be solved in polynomial time and if labels can occur up to three times, then the problem becomes NP-hard. Lastly, Reachable Object is the problem of deciding whether there is a sequence of rational trades of objects among agents such that a given agent can obtain a certain object. A rational trade is a swap of objects between two agents where both agents profit from the swap, that is, they receive objects they prefer over the objects they trade away. This problem can be seen as a natural generalization of the well-known and well-studied Housing Market problem where the agents are arranged in a graph and only neighboring agents can trade objects. We prove a dichotomy result that states that the problem is polynomial-time solvable if each agent prefers at most two objects over its initially held object and it is NP-hard if each agent prefers at most three objects over its initially held object. We also provide a polynomial-time 2-SAT program for the case where the graph of agents is a cycle. In dieser Arbeit entwickeln wir schnellere exakte Algorithmen (schneller bezüglich der Worst-Case-Laufzeit) für Spezialfälle von Graphproblemen. Diese Algorithmen beruhen größtenteils auf dynamischem Programmieren und auf 2-SAT-Programmierung. Dynamisches Programmieren beschreibt den Vorgang, ein Problem rekursiv in Unterprobleme zu zerteilen, sodass diese Unterprobleme gemeinsame Unterunterprobleme haben. Wenn diese Unterprobleme optimal gelöst wurden, dann kombiniert das dynamische Programm diese Lösungen zu einer optimalen Lösung des Ursprungsproblems. 2-SAT-Programmierung bezeichnet den Prozess, ein Problem durch eine Menge von 2-SAT-Formeln (aussagenlogische Formeln in konjunktiver Normalform, wobei jede Klausel aus maximal zwei Literalen besteht) auszudrücken. Dabei müssen erfüllende Wahrheitswertbelegungen für eine Teilmenge der 2-SAT-Formeln zu einer Lösung des Ursprungsproblems korrespondieren. Wenn eine 2-SAT-Formel erfüllbar ist, dann kann eine erfüllende Wahrheitswertbelegung in Linearzeit in der Länge der Formel berechnet werden. Wenn entsprechende 2-SAT-Formeln also in polynomieller Zeit in der Eingabegröße des Ursprungsproblems erstellt werden können, dann kann das Ursprungsproblem in polynomieller Zeit gelöst werden. Im folgenden beschreiben wir die Hauptresultate der Arbeit.Bei dem Diameter-Problem wird die größte Distanz zwischen zwei beliebigen Knoten in einem gegebenen ungerichteten Graphen gesucht. Das Ergebnis (der Durchmesser des Eingabegraphen) gehört zu den wichtigsten Parametern der Graphanalyse. In dieser Arbeit erzielen wir sowohl positive als auch negative Ergebnisse für Diameter. Wir konzentrieren uns dabei auf parametrisierte Algorithmen für Parameterkombinationen, die in vielen praktischen Anwendungen klein sind, und auf Parameter, die eine Distanz zur Trivialität messen.Bei dem Problem Length-Bounded Cut geht es darum, ob es eine Kantenmenge begrenzter Größe in einem Eingabegraphen gibt, sodass das Entfernen dieser Kanten die Distanz zwischen zwei gegebenen Knoten auf ein gegebenes Minimum erhöht. Wir bestätigen in dieser Arbeit eine Vermutung aus der wissenschaftlichen Literatur, dass Length-Bounded Cut in polynomieller Zeit in der Eingabegröße auf Einheitsintervallgraphen (Intervallgraphen, in denen jedes Intervall die gleiche Länge hat) gelöst werden kann. Der Algorithmus basiert auf dynamischem Programmieren.k-Disjoint Shortest Paths beschreibt das Problem, knotendisjunkte Pfade zwischen k gegebenen Knotenpaaren zu suchen, sodass jeder der k Pfade ein kürzester Pfad zwischen den jeweiligen Endknoten ist. Wir beschreiben ein dynamisches Programm mit einer Laufzeit n^O((k+1)!) für dieses Problem, wobei n die Anzahl der Knoten im Eingabegraphen ist. Dies zeigt, dass k-Disjoint Shortest Paths in polynomieller Zeit für jedes konstante k gelöst werden kann, was für über 20 Jahre ein ungelöstes Problem der algorithmischen Graphentheorie war.Das Problem Tree Containment fragt, ob ein gegebener phylogenetischer Baum T in einem gegebenen phylogenetischen Netzwerk N enthalten ist. Ein phylogenetisches Netzwerk (bzw. ein phylogenetischer Baum) ist ein gerichteter azyklischer Graph (bzw. ein gerichteter Baum) mit genau einer Quelle, in dem jeder Knoten höchstens eine ausgehende oder höchstens eine eingehende Kante hat und jedes Blatt eine Beschriftung trägt. Das Problem stammt aus der Bioinformatik aus dem Bereich der Suche nach dem Baums des Lebens (der Geschichte der Artenbildung). Wir führen eine neue Variante des Problems ein, die wir Soft Tree Containment nennen und die bestimmte Unsicherheitsfaktoren berücksichtigt. Wir zeigen mit Hilfe von 2-SAT-Programmierung, dass Soft Tree Containment in polynomieller Zeit gelöst werden kann, wenn N ein phylogenetischer Baum ist, in dem jeweils maximal zwei Blätter die gleiche Beschriftung tragen. Wir ergänzen dieses Ergebnis mit dem Beweis, dass Soft Tree Containment NP-schwer ist, selbst wenn N auf phylogenetische Bäume beschränkt ist, in denen jeweils maximal drei Blätter die gleiche Beschriftung tragen.Abschließend betrachten wir das Problem Reachable Object. Hierbei wird nach einer Sequenz von rationalen Tauschoperationen zwischen Agentinnen gesucht, sodass eine bestimmte Agentin ein bestimmtes Objekt erhält. Eine Tauschoperation ist rational, wenn beide an dem Tausch beteiligten Agentinnen ihr neues Objekt gegenüber dem jeweiligen alten Objekt bevorzugen. Reachable Object ist eine Verallgemeinerung des bekannten und viel untersuchten Problems Housing Market. Hierbei sind die Agentinnen in einem Graphen angeordnet und nur benachbarte Agentinnen können Objekte miteinander tauschen. Wir zeigen, dass Reachable Object NP-schwer ist, selbst wenn jede Agentin maximal drei Objekte gegenüber ihrem Startobjekt bevorzugt und dass Reachable Object polynomzeitlösbar ist, wenn jede Agentin maximal zwei Objekte gegenüber ihrem Startobjekt bevorzugt. Wir geben außerdem einen Polynomzeitalgorithmus für den Spezialfall an, in dem der Graph der Agentinnen ein Kreis ist. Dieser Polynomzeitalgorithmus basiert auf 2-SAT-Programmierung.


Book
Computational Biology and Chemistry
Authors: ---
Year: 2020 Publisher: London, England : IntechOpen,

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The use of computers and software tools in biochemistry (biology) has led to a deep revolution in basic sciences and medicine. Bioinformatics and systems biology are the direct results of this revolution. With the involvement of computers, software tools, and internet services in scientific disciplines comprising biology and chemistry, new terms, technologies, and methodologies appeared and established. Bioinformatic software tools, versatile databases, and easy internet access resulted in the occurrence of computational biology and chemistry. Today, we have new types of surveys and laboratories including "in silico studies" and "dry labs" in which bioinformaticians conduct their investigations to gain invaluable outcomes. These features have led to 3-dimensioned illustrations of different molecules and complexes to get a better understanding of nature.


Book
New Trends on Genome and Transcriptome Characterizations
Authors: ---
Year: 2018 Publisher: Frontiers Media SA

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This Research Topic is devoted to bioinformaticians, geneticists and researchers who study or apply methods and algorithms for genomes and transcriptome analyses, aimed at understanding pathology discriminations and classifications. Papers are encouraged that use unconventional approaches and/or where mathematical and computational concepts are applied to biological and medical contexts in original ways. The contributions presented in the Topic should be of interest also to a wide class of scientists and students involved in the several fields where genomic and transcriptomic approaches are becoming essential for future investigations.


Book
Systems Biology and the Challenge of Deciphering the Metabolic Mechanisms Underlying Cancer
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Year: 2017 Publisher: Frontiers Media SA

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Since the discovery of the Warburg effect in the 1920s cancer has been tightly associated with the genetic and metabolic state of the cell. One of the hallmarks of cancer is the alteration of the cellular metabolism in order to promote proliferation and undermine cellular defense mechanisms such as apoptosis or detection by the immune system. However, the strategies by which this is achieved in different cancers and sometimes even in different patients of the same cancer is very heterogeneous, which hinders the design of general treatment options.Recently, there has been an ongoing effort to study this phenomenon on a genomic scale in order to understand the causality underlying the disease. Hence, current “omics” technologies have contributed to identify and monitor different biological pieces at different biological levels, such as genes, proteins or metabolites. These technological capacities have provided us with vast amounts of clinical data where a single patient may often give rise to various tissue samples, each of them being characterized in detail by genomescale data on the sequence, expression, proteome and metabolome level. Data with such detail poses the imminent problem of extracting meaningful interpretations and translating them into specific treatment options. To this purpose, Systems Biology provides a set of promising computational tools in order to decipher the mechanisms driving a healthy cell’s metabolism into a cancerous one. However, this enterprise requires bridging the gap between large data resources, mathematical analysis and modeling specifically designed to work with the available data. This is by no means trivial and requires high levels of communication and adaptation between the experimental and theoretical side of research.


Book
Computational biology and applied bioinformatics
Authors: --- ---
ISBN: 953515544X 9533076291 Year: 2011 Publisher: IntechOpen

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Nowadays it is difficult to imagine an area of knowledge that can continue developing without the use of computers and informatics. It is not different with biology, that has seen an unpredictable growth in recent decades, with the rise of a new discipline, bioinformatics, bringing together molecular biology, biotechnology and information technology. More recently, the development of high throughput techniques, such as microarray, mass spectrometry and DNA sequencing, has increased the need of computational support to collect, store, retrieve, analyze, and correlate huge data sets of complex information. On the other hand, the growth of the computational power for processing and storage has also increased the necessity for deeper knowledge in the field. The development of bioinformatics has allowed now the emergence of systems biology, the study of the interactions between the components of a biological system, and how these interactions give rise to the function and behavior of a living being. This book presents some theoretical issues, reviews, and a variety of bioinformatics applications. For better understanding, the chapters were grouped in two parts. In Part I, the chapters are more oriented towards literature review and theoretical issues. Part II consists of application-oriented chapters that report case studies in which a specific biological problem is treated with bioinformatics tools.


Book
Systems and Computational Biology : Bioinformatics and Computational Modeling
Authors: ---
ISBN: 9535144391 9533078758 Year: 2011 Publisher: IntechOpen

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Whereas some ""microarray"" or ""bioinformatics"" scientists among us may have been criticized as doing ""cataloging research"", the majority of us believe that we are sincerely exploring new scientific and technological systems to benefit human health, human food and animal feed production, and environmental protections. Indeed, we are humbled by the complexity, extent and beauty of cross-talks in various biological systems; on the other hand, we are becoming more educated and are able to start addressing honestly and skillfully the various important issues concerning translational medicine, global agriculture, and the environment. The two volumes of this book present a series of high-quality research or review articles in a timely fashion to this emerging research field of our scientific community.


Book
Systems and Computational Biology : Molecular and Cellular Experimental Systems
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ISBN: 9535155474 9533072806 Year: 2011 Publisher: IntechOpen

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Whereas some "microarray" or "bioinformatics" scientists among us may have been criticized as doing "cataloging research", the majority of us believe that we are sincerely exploring new scientific and technological systems to benefit human health, human food and animal feed production, and environmental protections. Indeed, we are humbled by the complexity, extent and beauty of cross-talks in various biological systems; on the other hand, we are becoming more educated and are able to start addressing honestly and skillfully the various important issues concerning translational medicine, global agriculture, and the environment. The two volumes of this book presents a series of high-quality research or review articles in a timely fashion to this emerging research field of our scientific community.


Book
Bioinformatics : Trends and Methodologies
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ISBN: 9535155490 9533072822 Year: 2011 Publisher: IntechOpen

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Bioinformatics - Trends and Methodologies is a collection of different views on most recent topics and basic concepts in bioinformatics. This book suits young researchers who seek basic fundamentals of bioinformatic skills such as data mining, data integration, sequence analysis and gene expression analysis as well as scientists who are interested in current research in computational biology and bioinformatics including next generation sequencing, transcriptional analysis and drug design. Because of the rapid development of new technologies in molecular biology, new bioinformatic techniques emerge accordingly to keep the pace of in silico development of life science. This book focuses partly on such new techniques and their applications in biomedical science. These techniques maybe useful in identification of some diseases and cellular disorders and narrow down the number of experiments required for medical diagnostic.


Book
Precision Medicine in Oncology
Authors: --- --- ---
Year: 2019 Publisher: Frontiers Media SA

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The emerging precision medicine approach aims to tailor disease prevention and treatment to each patient on the basis of individual variability, environmental factors and lifestyle. Fundamental achievements in the last few decades have converged to offer nowadays the compelling opportunity to move towards this innovative approach: i) unprecedented improvements in disease modeling in silico, in vitro and in vivo; ii) acquisition of a wide range of biomedical information combined with the development of computational toolsets for flexible and integrative analyses of multi-assay datasets. Our deeper understanding of oncogenic mechanisms has finally begun to have a crucial impact on clinical decisions at several steps, from cancer prevention and diagnosis to therapeutic intervention. However, precision oncology still encounters several unresolved hurdles including tumour heterogeneity and recurrence as well as unexplained drug resistance and lack of effective ways to monitor response to therapeutic treatments. Notably, limitations in biomedical research regulation and governance represent additional debatable issues that need careful consideration.

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