Computational Molecular Biology

Computational Biology is a fairly new subject that arose in response to the computational problems posed by the analysis and the processing of biomolecular sequence and structure data. The field was initiated in the late 60's and early 70's largely by pioneers working in the life sciences. Physicists and mathematicians entered the field in the 70's and 80's, while Computer Science became involved with the new biological problems in the late 1980's. Computational problems have gained further importance in molecular biology through the various genome projects which produce enormous amounts of data. For this bibliography we focus on those areas of computational molecular biology that involve discrete algorithms or discrete optimization. We thus neglect several other areas of computational molecular biology, like most of the literature on the protein folding problem, as well as databases for molecular and genetic data, and genetic mapping algorithms. Due to the availability of review papers and a bibliography this bibliography

QuASeR -- Quantum Accelerated De Novo DNA Sequence Reconstruction

In this article, we present QuASeR, a reference-free DNA sequence reconstruction implementation via de novo assembly on both gate-based and quantum annealing platforms. Each one of the four steps of the implementation (TSP, QUBO, Hamiltonians and QAOA) is explained with simple proof-of-concept examples to target both the genomics research community and quantum application developers in a self-contained manner. The details of the implementation are discussed for the various layers of the quantum full-stack accelerator design. We also highlight the limitations of current classical simulation and available quantum hardware systems. The implementation is open-source and can be found on https://github.com/prince-ph0en1x/QuASeR.Comment: 24 page

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

An Approximation Algorithm for the Exact Matching Problem in Bipartite Graphs

In 1982 Papadimitriou and Yannakakis introduced the Exact Matching problem, in which given a red and blue edge-colored graph G and an integer k one has to decide whether there exists a perfect matching in G with exactly k red edges. Even though a randomized polynomial-time algorithm for this problem was quickly found a few years later, it is still unknown today whether a deterministic polynomial-time algorithm exists. This makes the Exact Matching problem an important candidate to test the RP=P hypothesis. In this paper we focus on approximating Exact Matching. While there exists a simple algorithm that computes in deterministic polynomial-time an almost perfect matching with exactly k red edges, not a lot of work focuses on computing perfect matchings with almost k red edges. In fact such an algorithm for bipartite graphs running in deterministic polynomial-time was published only recently (STACS\u2723). It outputs a perfect matching with k\u27 red edges with the guarantee that 0.5k ? k\u27 ? 1.5k. In the present paper we aim at approximating the number of red edges without exceeding the limit of k red edges. We construct a deterministic polynomial-time algorithm, which on bipartite graphs computes a perfect matching with k\u27 red edges such that k/3 ? k\u27 ? k

Transcript assembly and abundance estimation with high-throughput RNA sequencing

We present algorithms and statistical methods for the reconstruction and abundance estimation of transcript sequences from high throughput RNA sequencing ("RNA-Seq"). We evaluate these approaches through large-scale experiments of a well studied model of muscle development. We begin with an overview of sequencing assays and outline why the short read alignment problem is fundamental to the analysis of these assays. We then describe two approaches to the contiguous alignment problem, one of which uses massively parallel graphics hardware to accelerate alignment, and one of which exploits an indexing scheme based on the Burrows-Wheeler transform. We then turn to the spliced alignment problem, which is fundamental to RNA-Seq, and present an algorithm, TopHat. TopHat is the first algorithm that can align the reads from an entire RNA-Seq experiment to a large genome without the aid of reference gene models. In the second part of the thesis, we present the first comparative RNA-Seq as- sembly algorithm, Cufflinks, which is adapted from a constructive proof of Dilworth's Theorem, a classic result in combinatorics. We evaluate Cufflinks by assembling the transcriptome from a time course RNA-Seq experiment of developing skeletal muscle cells. The assembly contains 13,689 known transcripts and 3,724 novel ones. Of the novel transcripts, 62% were strongly supported by earlier sequencing experiments or by homologous transcripts in other organisms. We further validated interesting genes with isoform-specific RT-PCR. We then present a statistical model for RNA-Seq included in Cufflinks and with which we estimate abundances of transcripts from RNA-seq data. Simulation studies demonstrate that the model is highly accurate. We apply this model to the muscle data, and track the abundances of individual isoforms over development. Finally, we present significance tests for changes in relative and absolute abundances between time points, which we employ to uncover differential expression and differential regulation. By testing for relative abundance changes within and between transcripts sharing a transcription start site, we find significant shifts in the rates of alternative splicing and promoter preference in hundreds of genes, including those believed to regulate muscle development

Exact Matching: Correct Parity and FPT Parameterized by Independence Number

Given an integer $k$ and a graph where every edge is colored either red or blue, the goal of the exact matching problem is to find a perfect matching with the property that exactly $k$ of its edges are red. Soon after Papadimitriou and Yannakakis (JACM 1982) introduced the problem, a randomized polynomial-time algorithm solving the problem was described by Mulmuley et al. (Combinatorica 1987). Despite a lot of effort, it is still not known today whether a deterministic polynomial-time algorithm exists. This makes the exact matching problem an important candidate to test the popular conjecture that the complexity classes P and RP are equal. In a recent article (MFCS 2022), progress was made towards this goal by showing that for bipartite graphs of bounded bipartite independence number, a polynomial time algorithm exists. In terms of parameterized complexity, this algorithm was an XP-algorithm parameterized by the bipartite independence number. In this article, we introduce novel algorithmic techniques that allow us to obtain an FPT-algorithm. If the input is a general graph we show that one can at least compute a perfect matching $M$ which has the correct number of red edges modulo 2, in polynomial time. This is motivated by our last result, in which we prove that an FPT algorithm for general graphs, parameterized by the independence number, reduces to the problem of finding in polynomial time a perfect matching $M$ with at most $k$ red edges and the correct number of red edges modulo 2

Codes for DNA Storage Channels

We consider the problem of assembling a sequence based on a collection of its substrings observed through a noisy channel. The mathematical basis of the problem is the construction and design of sequences that may be discriminated based on a collection of their substrings observed through a noisy channel. We explain the connection between the sequence reconstruction problem and the problem of DNA synthesis and sequencing, and introduce the notion of a DNA storage channel. We analyze the number of sequence equivalence classes under the channel mapping and propose new asymmetric coding techniques to combat the effects of synthesis and sequencing noise. In our analysis, we make use of restricted de Bruijn graphs and Ehrhart theory for rational polytopes.Comment: 32 pages, 5 figure

Discovery of Unconventional Patterns for Sequence Analysis: Theory and Algorithms

The biology community is collecting a large amount of raw data, such as the genome sequences of organisms, microarray data, interaction data such as gene-protein interactions, protein-protein interactions, etc. This amount is rapidly increasing and the process of understanding the data is lagging behind the process of acquiring it. An inevitable first step towards making sense of the data is to study their regularities focusing on the non-random structures appearing surprisingly often in the input sequences: patterns. In this thesis we discuss three incarnations of the pattern discovery task, exploring three types of patterns that can model different regularities of the input dataset. While mask patterns have been designed to model short repeated biological sequences, showing a high conservation of their content at some specific positions, permutation patterns have been designed to detect repeated patterns whose parts maintain their physical adjacency but not their ordering in all the pattern occurrences. Transposons, instead, model mobile sequences in the input dataset, which can be discovered by comparing different copies of the same input string, detecting large insertions and deletions in their alignment

Analysis Of DNA Motifs In The Human Genome

DNA motifs include repeat elements, promoter elements and gene regulator elements, and play a critical role in the human genome. This thesis describes a genome-wide computational study on two groups of motifs: tandem repeats and core promoter elements. Tandem repeats in DNA sequences are extremely relevant in biological phenomena and diagnostic tools. Computational programs that discover tandem repeats generate a huge volume of data, which can be difficult to decipher without further organization. A new method is presented here to organize and rank detected tandem repeats through clustering and classification. Our work presents multiple ways of expressing tandem repeats using the n-gram model with different clustering distance measures. Analysis of the clusters for the tandem repeats in the human genome shows that the method yields a well-defined grouping in which similarity among repeats is apparent. Our new, alignment-free method facilitates the analysis of the myriad of tandem repeats replete in the human genome. We believe that this work will lead to new discoveries on the roles, origins, and significance of tandem repeats. As with tandem repeats, promoter sequences of genes contain binding sites for proteins that play critical roles in mediating expression levels. Promoter region binding proteins and their co-factors influence timing and context of transcription. Despite the critical regulatory role of these non-coding sequences, computational methods to identify and predict DNA binding sites are extremely limited. The work reported here analyzes the relative occurrence of core promoter elements (CPEs) in and around transcription start sites. We found that out of all the data sets 49\%-63\% upstream regions have either TATA box or DPE elements. Our results suggest the possibility of predicting transcription start sites through combining CPEs signals with other promoter signals such as CpG islands and clusters of specific transcription binding sites