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LIPIcs, Volume 172
20th International Workshop on Algorithms in Bioinformatics (WABI 2020)
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Leibniz International Proceedings in Informatics (LIPIcs)
Conference: International Workshop on Algorithms in Bioinformatics (WABI)
Publication Details
- published at: 2020-08-25
- Publisher: Schloss Dagstuhl – Leibniz-Zentrum für Informatik
- ISBN: 978-3-95977-161-0
- DBLP: db/conf/wabi/wabi2020
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Complete Volume
LIPIcs, Volume 172, WABI 2020, Complete Volume
Abstract
LIPIcs, Volume 172, WABI 2020, Complete Volume
Cite as
20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 1-360, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@Proceedings{kingsford_et_al:LIPIcs.WABI.2020,
title = {{LIPIcs, Volume 172, WABI 2020, Complete Volume}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {1--360},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020},
URN = {urn:nbn:de:0030-drops-127881},
doi = {10.4230/LIPIcs.WABI.2020},
annote = {Keywords: LIPIcs, Volume 172, WABI 2020, Complete Volume}
}
Document
Front Matter
Front Matter, Table of Contents, Preface, Conference Organization
Abstract
Front Matter, Table of Contents, Preface, Conference Organization
Cite as
20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 0:i-0:x, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{kingsford_et_al:LIPIcs.WABI.2020.0,
author = {Kingsford, Carl and Pisanti, Nadia},
title = {{Front Matter, Table of Contents, Preface, Conference Organization}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {0:i--0:x},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.0},
URN = {urn:nbn:de:0030-drops-127891},
doi = {10.4230/LIPIcs.WABI.2020.0},
annote = {Keywords: Front Matter, Table of Contents, Preface, Conference Organization}
}
Document
Approximate Search for Known Gene Clusters in New Genomes Using PQ-Trees
Abstract
We define a new problem in comparative genomics, denoted PQ-Tree Search, that takes as input a PQ-tree T representing the known gene orders of a gene cluster of interest, a gene-to-gene substitution scoring function h, integer parameters d_T and d_S, and a new genome S. The objective is to identify in S approximate new instances of the gene cluster that could vary from the known gene orders by genome rearrangements that are constrained by T, by gene substitutions that are governed by h, and by gene deletions and insertions that are bounded from above by d_T and d_S, respectively. We prove that the PQ-Tree Search problem is NP-hard and propose a parameterized algorithm that solves the optimization variant of PQ-Tree Search in O^*(2^{γ}) time, where γ is the maximum degree of a node in T and O^* is used to hide factors polynomial in the input size.
The algorithm is implemented as a search tool, denoted PQFinder, and applied to search for instances of chromosomal gene clusters in plasmids, within a dataset of 1,487 prokaryotic genomes. We report on 29 chromosomal gene clusters that are rearranged in plasmids, where the rearrangements are guided by the corresponding PQ-tree. One of these results, coding for a heavy metal efflux pump, is further analysed to exemplify how PQFinder can be harnessed to reveal interesting new structural variants of known gene clusters.
Cite as
Galia R. Zimerman, Dina Svetlitsky, Meirav Zehavi, and Michal Ziv-Ukelson. Approximate Search for Known Gene Clusters in New Genomes Using PQ-Trees. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 1:1-1:24, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{zimerman_et_al:LIPIcs.WABI.2020.1,
author = {Zimerman, Galia R. and Svetlitsky, Dina and Zehavi, Meirav and Ziv-Ukelson, Michal},
title = {{Approximate Search for Known Gene Clusters in New Genomes Using PQ-Trees}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {1:1--1:24},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.1},
URN = {urn:nbn:de:0030-drops-127906},
doi = {10.4230/LIPIcs.WABI.2020.1},
annote = {Keywords: PQ-Tree, Gene Cluster, Efflux Pump}
}
Document
An Interpretable Classification Method for Predicting Drug Resistance in M. Tuberculosis
Abstract
Motivation: The prediction of drug resistance and the identification of its mechanisms in bacteria such as Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a challenging problem. Modern methods based on testing against a catalogue of previously identified mutations often yield poor predictive performance. On the other hand, machine learning techniques have demonstrated high predictive accuracy, but many of them lack interpretability to aid in identifying specific mutations which lead to resistance. We propose a novel technique, inspired by the group testing problem and Boolean compressed sensing, which yields highly accurate predictions and interpretable results at the same time.
Results: We develop a modified version of the Boolean compressed sensing problem for identifying drug resistance, and implement its formulation as an integer linear program. This allows us to characterize the predictive accuracy of the technique and select an appropriate metric to optimize. A simple adaptation of the problem also allows us to quantify the sensitivity-specificity trade-off of our model under different regimes. We test the predictive accuracy of our approach on a variety of commonly used antibiotics in treating tuberculosis and find that it has accuracy comparable to that of standard machine learning models and points to several genes with previously identified association to drug resistance.
Cite as
Hooman Zabeti, Nick Dexter, Amir Hosein Safari, Nafiseh Sedaghat, Maxwell Libbrecht, and Leonid Chindelevitch. An Interpretable Classification Method for Predicting Drug Resistance in M. Tuberculosis. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 2:1-2:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{zabeti_et_al:LIPIcs.WABI.2020.2,
author = {Zabeti, Hooman and Dexter, Nick and Safari, Amir Hosein and Sedaghat, Nafiseh and Libbrecht, Maxwell and Chindelevitch, Leonid},
title = {{An Interpretable Classification Method for Predicting Drug Resistance in M. Tuberculosis}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {2:1--2:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.2},
URN = {urn:nbn:de:0030-drops-127911},
doi = {10.4230/LIPIcs.WABI.2020.2},
annote = {Keywords: Drug resistance, whole-genome sequencing, interpretable machine learning, integer linear programming, rule-based learning}
}
Document
Natural Family-Free Genomic Distance
Abstract
A classical problem in comparative genomics is to compute the rearrangement distance, that is the minimum number of large-scale rearrangements required to transform a given genome into another given genome. While the most traditional approaches in this area are family-based, i.e., require the classification of DNA fragments of both genomes into families, more recently an alternative model was proposed, which, instead of family classification, simply uses the pairwise similarities between DNA fragments of both genomes to compute their rearrangement distance. This model represents structural rearrangements by the generic double cut and join (DCJ) operation and is then called family-free DCJ distance. It computes the DCJ distance between the two genomes by searching for a matching of their genes based on the given pairwise similarities, therefore helping to find gene homologies. The drawback is that its computation is NP-hard. Another point is that the family-free DCJ distance must correspond to a maximal matching of the genes, due to the fact that unmatched genes are just ignored: maximizing the matching prevents the free lunch artifact of having empty or almost empty matchings giving the smaller distances.
In this paper, besides DCJ operations, we allow content-modifying operations of insertions and deletions of DNA segments and propose a new and more general family-free genomic distance. In our model we use the pairwise similarities to assign weights to both matched and unmatched genes, so that an optimal solution does not necessarily maximize the matching. Our model then results in a natural family-free genomic distance, that takes into consideration all given genes and has a search space composed of matchings of any size. We provide an efficient ILP formulation to solve it, by extending the previous formulations for computing family-based genomic distances from Shao et al. (J. Comput. Biol., 2015) and Bohnenkämper et al. (Proc. of RECOMB, 2020). Our experiments show that the ILP can handle not only bacterial genomes, but also fungi and insects, or sets of chromosomes of mammals and plants. In a comparison study of six fruit fly genomes, we obtained accurate results.
Cite as
Diego P. Rubert, Fábio V. Martinez, and Marília D. V. Braga. Natural Family-Free Genomic Distance. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 3:1-3:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{rubert_et_al:LIPIcs.WABI.2020.3,
author = {Rubert, Diego P. and Martinez, F\'{a}bio V. and Braga, Mar{\'\i}lia D. V.},
title = {{Natural Family-Free Genomic Distance}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {3:1--3:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.3},
URN = {urn:nbn:de:0030-drops-127926},
doi = {10.4230/LIPIcs.WABI.2020.3},
annote = {Keywords: Comparative genomics, Genome rearrangement, DCJ-indel distance}
}
Document
Fast Lightweight Accurate Xenograft Sorting
Abstract
Motivation: With an increasing number of patient-derived xenograft (PDX) models being created and subsequently sequenced to study tumor heterogeneity and to guide therapy decisions, there is a similarly increasing need for methods to separate reads originating from the graft (human) tumor and reads originating from the host species' (mouse) surrounding tissue. Two kinds of methods are in use: On the one hand, alignment-based tools require that reads are mapped and aligned (by an external mapper/aligner) to the host and graft genomes separately first; the tool itself then processes the resulting alignments and quality metrics (typically BAM files) to assign each read or read pair. On the other hand, alignment-free tools work directly on the raw read data (typically FASTQ files). Recent studies compare different approaches and tools, with varying results.
Results: We show that alignment-free methods for xenograft sorting are superior concerning CPU time usage and equivalent in accuracy. We improve upon the state of the art by presenting a fast lightweight approach based on three-way bucketed quotiented Cuckoo hashing. Our hash table requires memory comparable to an FM index typically used for read alignment and less than other alignment-free approaches. It allows extremely fast lookups and uses less CPU time than other alignment-free methods and alignment-based methods at similar accuracy.
Cite as
Jens Zentgraf and Sven Rahmann. Fast Lightweight Accurate Xenograft Sorting. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 4:1-4:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{zentgraf_et_al:LIPIcs.WABI.2020.4,
author = {Zentgraf, Jens and Rahmann, Sven},
title = {{Fast Lightweight Accurate Xenograft Sorting}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {4:1--4:16},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.4},
URN = {urn:nbn:de:0030-drops-127933},
doi = {10.4230/LIPIcs.WABI.2020.4},
annote = {Keywords: xenograft sorting, alignment-free method, Cuckoo hashing, k-mer}
}
Document
Phyolin: Identifying a Linear Perfect Phylogeny in Single-Cell DNA Sequencing Data of Tumors
Abstract
Cancer arises from an evolutionary process where somatic mutations occur and eventually give rise to clonal expansions. Modeling this evolutionary process as a phylogeny is useful for treatment decision-making as well as understanding evolutionary patterns across patients and cancer types. However, cancer phylogeny inference from single-cell DNA sequencing data of tumors is challenging due to limitations with sequencing technology and the complexity of the resulting problem. Therefore, as a first step some value might be obtained from correctly classifying the evolutionary process as either linear or branched. The biological implications of these two high-level patterns are different and understanding what cancer types and which patients have each of these trajectories could provide useful insight for both clinicians and researchers. Here, we introduce the Linear Perfect Phylogeny Flipping Problem as a means of testing a null model that the tree topology is linear and show that it is NP-hard. We develop Phyolin and, through both in silico experiments and real data application, show that it is an accurate, easy to use and a reasonably fast method for classifying an evolutionary trajectory as linear or branched.
Cite as
Leah L. Weber and Mohammed El-Kebir. Phyolin: Identifying a Linear Perfect Phylogeny in Single-Cell DNA Sequencing Data of Tumors. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 5:1-5:14, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{weber_et_al:LIPIcs.WABI.2020.5,
author = {Weber, Leah L. and El-Kebir, Mohammed},
title = {{Phyolin: Identifying a Linear Perfect Phylogeny in Single-Cell DNA Sequencing Data of Tumors}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {5:1--5:14},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.5},
URN = {urn:nbn:de:0030-drops-127946},
doi = {10.4230/LIPIcs.WABI.2020.5},
annote = {Keywords: Constraint programming, intra-tumor heterogeneity, combinatorial optimization}
}
Document
The Longest Run Subsequence Problem
Abstract
Genome assembly is one of the most important problems in computational genomics. Here, we suggest addressing the scaffolding phase, in which contigs need to be linked and ordered to obtain larger pseudo-chromosomes, by means of a second incomplete assembly of a related species. The idea is to use alignments of binned regions in one contig to find the most homologous contig in the other assembly. We show that ordering the contigs of the other assembly can be expressed by a new string problem, the longest run subsequence problem (LRS). We show that LRS is NP-hard and present reduction rules and two algorithmic approaches that, together, are able to solve large instances of LRS to provable optimality. In particular, they can solve realistic instances resulting from partial Arabidopsis thaliana assemblies in short computation time. Our source code and all data used in the experiments are freely available.
Cite as
Sven Schrinner, Manish Goel, Michael Wulfert, Philipp Spohr, Korbinian Schneeberger, and Gunnar W. Klau. The Longest Run Subsequence Problem. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 6:1-6:13, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{schrinner_et_al:LIPIcs.WABI.2020.6,
author = {Schrinner, Sven and Goel, Manish and Wulfert, Michael and Spohr, Philipp and Schneeberger, Korbinian and Klau, Gunnar W.},
title = {{The Longest Run Subsequence Problem}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {6:1--6:13},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.6},
URN = {urn:nbn:de:0030-drops-127951},
doi = {10.4230/LIPIcs.WABI.2020.6},
annote = {Keywords: alignments, assembly, string algorithm, longest subsequence}
}
Document
Linear Time Construction of Indexable Founder Block Graphs
Abstract
We introduce a compact pangenome representation based on an optimal segmentation concept that aims to reconstruct founder sequences from a multiple sequence alignment (MSA). Such founder sequences have the feature that each row of the MSA is a recombination of the founders. Several linear time dynamic programming algorithms have been previously devised to optimize segmentations that induce founder blocks that then can be concatenated into a set of founder sequences. All possible concatenation orders can be expressed as a founder block graph. We observe a key property of such graphs: if the node labels (founder segments) do not repeat in the paths of the graph, such graphs can be indexed for efficient string matching. We call such graphs segment repeat-free founder block graphs.
We give a linear time algorithm to construct a segment repeat-free founder block graph given an MSA. The algorithm combines techniques from the founder segmentation algorithms (Cazaux et al. SPIRE 2019) and fully-functional bidirectional Burrows-Wheeler index (Belazzougui and Cunial, CPM 2019). We derive a succinct index structure to support queries of arbitrary length in the paths of the graph.
Experiments on an MSA of SARS-CoV-2 strains are reported. An MSA of size 410× 29811 is compacted in one minute into a segment repeat-free founder block graph of 3900 nodes and 4440 edges. The maximum length and total length of node labels is 12 and 34968, respectively. The index on the graph takes only 3% of the size of the MSA.
Cite as
Veli Mäkinen, Bastien Cazaux, Massimo Equi, Tuukka Norri, and Alexandru I. Tomescu. Linear Time Construction of Indexable Founder Block Graphs. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 7:1-7:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{makinen_et_al:LIPIcs.WABI.2020.7,
author = {M\"{a}kinen, Veli and Cazaux, Bastien and Equi, Massimo and Norri, Tuukka and Tomescu, Alexandru I.},
title = {{Linear Time Construction of Indexable Founder Block Graphs}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {7:1--7:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.7},
URN = {urn:nbn:de:0030-drops-127961},
doi = {10.4230/LIPIcs.WABI.2020.7},
annote = {Keywords: Pangenome indexing, founder reconstruction, multiple sequence alignment, compressed data structures, string matching}
}
Document
GraphBin2: Refined and Overlapped Binning of Metagenomic Contigs Using Assembly Graphs
Abstract
Metagenomic sequencing allows us to study structure, diversity and ecology in microbial communities without the necessity of obtaining pure cultures. In many metagenomics studies, the reads obtained from metagenomics sequencing are first assembled into longer contigs and these contigs are then binned into clusters of contigs where contigs in a cluster are expected to come from the same species. As different species may share common sequences in their genomes, one assembled contig may belong to multiple species. However, existing tools for contig binning only support non-overlapped binning, i.e., each contig is assigned to at most one bin (species). In this paper, we introduce GraphBin2 which refines the binning results obtained from existing tools and, more importantly, is able to assign contigs to multiple bins. GraphBin2 uses the connectivity and coverage information from assembly graphs to adjust existing binning results on contigs and to infer contigs shared by multiple species. Experimental results on both simulated and real datasets demonstrate that GraphBin2 not only improves binning results of existing tools but also supports to assign contigs to multiple bins.
Cite as
Vijini G. Mallawaarachchi, Anuradha S. Wickramarachchi, and Yu Lin. GraphBin2: Refined and Overlapped Binning of Metagenomic Contigs Using Assembly Graphs. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 8:1-8:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{mallawaarachchi_et_al:LIPIcs.WABI.2020.8,
author = {Mallawaarachchi, Vijini G. and Wickramarachchi, Anuradha S. and Lin, Yu},
title = {{GraphBin2: Refined and Overlapped Binning of Metagenomic Contigs Using Assembly Graphs}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {8:1--8:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.8},
URN = {urn:nbn:de:0030-drops-127974},
doi = {10.4230/LIPIcs.WABI.2020.8},
annote = {Keywords: Metagenomics binning, contigs, assembly graphs, overlapped binning}
}
Document
Fast and Efficient Rmap Assembly Using the Bi-Labelled de Bruijn Graph
Abstract
Genome wide optical maps are high resolution restriction maps that give a unique numeric representation to a genome. They are produced by assembling hundreds of thousands of single molecule optical maps, which are called Rmaps. Unfortunately, there exists very few choices for assembling Rmap data. There exists only one publicly-available non-proprietary method for assembly and one proprietary method that is available via an executable. Furthermore, the publicly-available method, by Valouev et al. (2006), follows the overlap-layout-consensus (OLC) paradigm, and therefore, is unable to scale for relatively large genomes. The algorithm behind the proprietary method, Bionano Genomics' Solve, is largely unknown. In this paper, we extend the definition of bi-labels in the paired de Bruijn graph to the context of optical mapping data, and present the first de Bruijn graph based method for Rmap assembly. We implement our approach, which we refer to as rmapper, and compare its performance against the assembler of Valouev et al. (2006) and Solve by Bionano Genomics on data from three genomes - E. coli, human, and climbing perch fish (Anabas Testudineus). Our method was the only one able to successfully run on all three genomes. The method of Valouev et al. (2006) only successfully ran on E. coli and Bionano Solve successfully ran on E. coli and human but not on the fish genome. Moreover, on the human genome rmapper was at least 130 times faster than Bionano Solve, used five times less memory and produced the highest genome fraction with zero mis-assemblies.
Cite as
Kingshuk Mukherjee, Massimiliano Rossi, Leena Salmela, and Christina Boucher. Fast and Efficient Rmap Assembly Using the Bi-Labelled de Bruijn Graph. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 9:1-9:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{mukherjee_et_al:LIPIcs.WABI.2020.9,
author = {Mukherjee, Kingshuk and Rossi, Massimiliano and Salmela, Leena and Boucher, Christina},
title = {{Fast and Efficient Rmap Assembly Using the Bi-Labelled de Bruijn Graph}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {9:1--9:16},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.9},
URN = {urn:nbn:de:0030-drops-127982},
doi = {10.4230/LIPIcs.WABI.2020.9},
annote = {Keywords: optical maps, de Bruijn graph, assembly}
}
Document
Economic Genome Assembly from Low Coverage Illumina and Nanopore Data
Abstract
Ongoing developments in genome sequencing have caused a fundamental paradigm shift in the field in recent years. With ever lower sequencing costs, projects are no longer limited by available raw data, but rather by computational demands. The high complexity of eukaryotic genomes in concordance with increasing data sizes creates unique demands on methods to assemble full genomes. We describe a new approach to assemble genomes from a combination of low-coverage short and long reads. LazyB starts from a bipartite overlap graph between long reads and restrictively filtered short-read unitigs, which are then reduced to a long-read overlap graph G. Instead of the more conventional approach of removing tips, bubbles, and other local features, LazyB stepwisely extracts subgraphs whose global properties approach a disjoint union of paths. First, a consistently oriented subgraph is extracted, which in a second step is reduced to a directed acyclic graph. In the next step, properties of proper interval graphs are used to extract contigs as maximum weight paths. These are translated into genomic sequences only in the final step. A prototype implementation of LazyB, entirely written in python, not only yields significantly more accurate assemblies of the yeast and fruit fly genomes compared to state-of-the-art pipelines but also requires much less computational effort. Our findings demonstrate a new low-cost method that enables the assembly of even large genomes with low computational effort.
Cite as
Thomas Gatter, Sarah von Löhneysen, Polina Drozdova, Tom Hartmann, and Peter F. Stadler. Economic Genome Assembly from Low Coverage Illumina and Nanopore Data. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 10:1-10:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{gatter_et_al:LIPIcs.WABI.2020.10,
author = {Gatter, Thomas and von L\"{o}hneysen, Sarah and Drozdova, Polina and Hartmann, Tom and Stadler, Peter F.},
title = {{Economic Genome Assembly from Low Coverage Illumina and Nanopore Data}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {10:1--10:22},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.10},
URN = {urn:nbn:de:0030-drops-127991},
doi = {10.4230/LIPIcs.WABI.2020.10},
annote = {Keywords: Nanopore sequencing, Illumina sequencing, genome assembly, spanning tree, unitigs, anchors}
}
Document
A Graph-Theoretic Barcode Ordering Model for Linked-Reads
Abstract
Considering a set of intervals on the real line, an interval graph records these intervals as nodes and their intersections as edges. Identifying (i.e. merging) pairs of nodes in an interval graph results in a multiple-interval graph. Given only the nodes and the edges of the multiple-interval graph without knowing the underlying intervals, we are interested in the following questions. Can one determine how many intervals correspond to each node? Can one compute a walk over the multiple-interval graph nodes that reflects the ordering of the original intervals? These questions are closely related to linked-read DNA sequencing, where barcodes are assigned to long molecules whose intersection graph forms an interval graph. Each barcode may correspond to multiple molecules, which complicates downstream analysis, and corresponds to the identification of nodes of the corresponding interval graph. Resolving the above graph-theoretic problems would facilitate analyses of linked-reads sequencing data, through enabling the conceptual separation of barcodes into molecules and providing, through the molecules order, a skeleton for accurately assembling the genome. Here, we propose a framework that takes as input an arbitrary intersection graph (such as an overlap graph of barcodes) and constructs a heuristic approximation of the ordering of the original intervals.
Cite as
Yoann Dufresne, Chen Sun, Pierre Marijon, Dominique Lavenier, Cedric Chauve, and Rayan Chikhi. A Graph-Theoretic Barcode Ordering Model for Linked-Reads. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 11:1-11:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{dufresne_et_al:LIPIcs.WABI.2020.11,
author = {Dufresne, Yoann and Sun, Chen and Marijon, Pierre and Lavenier, Dominique and Chauve, Cedric and Chikhi, Rayan},
title = {{A Graph-Theoretic Barcode Ordering Model for Linked-Reads}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {11:1--11:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.11},
URN = {urn:nbn:de:0030-drops-128001},
doi = {10.4230/LIPIcs.WABI.2020.11},
annote = {Keywords: DNA sequencing, graph algorithms, linked-reads, interval graphs, cliques}
}
Document
Exact Transcript Quantification Over Splice Graphs
Abstract
The probability of sequencing a set of RNA-seq reads can be directly modeled using the abundances of splice junctions in splice graphs instead of the abundances of a list of transcripts. We call this model graph quantification, which was first proposed by Bernard et al. (2014). The model can be viewed as a generalization of transcript expression quantification where every full path in the splice graph is a possible transcript. However, the previous graph quantification model assumes the length of single-end reads or paired-end fragments is fixed. We provide an improvement of this model to handle variable-length reads or fragments and incorporate bias correction. We prove that our model is equivalent to running a transcript quantifier with exactly the set of all compatible transcripts. The key to our method is constructing an extension of the splice graph based on Aho-Corasick automata. The proof of equivalence is based on a novel reparameterization of the read generation model of a state-of-art transcript quantification method. This new approach is useful for modeling scenarios where reference transcriptome is incomplete or not available and can be further used in transcriptome assembly or alternative splicing analysis.
Cite as
Cong Ma, Hongyu Zheng, and Carl Kingsford. Exact Transcript Quantification Over Splice Graphs. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 12:1-12:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{ma_et_al:LIPIcs.WABI.2020.12,
author = {Ma, Cong and Zheng, Hongyu and Kingsford, Carl},
title = {{Exact Transcript Quantification Over Splice Graphs}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {12:1--12:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.12},
URN = {urn:nbn:de:0030-drops-128013},
doi = {10.4230/LIPIcs.WABI.2020.12},
annote = {Keywords: RNA-seq, alternative splicing, transcript quantification, splice graph, network flow}
}
Document
Shape Decomposition Algorithms for Laser Capture Microdissection
Abstract
In the context of biomarker discovery and molecular characterization of diseases, laser capture microdissection is a highly effective approach to extract disease-specific regions from complex, heterogeneous tissue samples. These regions have to be decomposed into feasible fragments as they have to satisfy certain constraints in size and morphology for the extraction to be successful. We model this problem of constrained shape decomposition as the computation of optimal feasible decompositions of simple polygons. We use a skeleton-based approach and present an algorithmic framework that allows the implementation of various feasibility criteria as well as optimization goals. Motivated by our application, we consider different constraints and examine the resulting fragmentations. Furthermore, we apply our method to lung tissue samples and show its advantages in comparison to a heuristic decomposition approach.
Cite as
Leonie Selbach, Tobias Kowalski, Klaus Gerwert, Maike Buchin, and Axel Mosig. Shape Decomposition Algorithms for Laser Capture Microdissection. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 13:1-13:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{selbach_et_al:LIPIcs.WABI.2020.13,
author = {Selbach, Leonie and Kowalski, Tobias and Gerwert, Klaus and Buchin, Maike and Mosig, Axel},
title = {{Shape Decomposition Algorithms for Laser Capture Microdissection}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {13:1--13:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.13},
URN = {urn:nbn:de:0030-drops-128020},
doi = {10.4230/LIPIcs.WABI.2020.13},
annote = {Keywords: Laser capture microdissection, shape decomposition, skeletonization}
}
Document
The Bourque Distances for Mutation Trees of Cancers
Abstract
Mutation trees are rooted trees of arbitrary node degree in which each node is labeled with a mutation set. These trees, also referred to as clonal trees, are used in computational oncology to represent the mutational history of tumours. Classical tree metrics such as the popular Robinson - Foulds distance are of limited use for the comparison of mutation trees. One reason is that mutation trees inferred with different methods or for different patients often contain different sets of mutation labels. Here, we generalize the Robinson - Foulds distance into a set of distance metrics called Bourque distances for comparing mutation trees. A connection between the Robinson - Foulds distance and the nearest neighbor interchange distance is also presented.
Cite as
Katharina Jahn, Niko Beerenwinkel, and Louxin Zhang. The Bourque Distances for Mutation Trees of Cancers. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 14:1-14:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{jahn_et_al:LIPIcs.WABI.2020.14,
author = {Jahn, Katharina and Beerenwinkel, Niko and Zhang, Louxin},
title = {{The Bourque Distances for Mutation Trees of Cancers}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {14:1--14:22},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.14},
URN = {urn:nbn:de:0030-drops-128039},
doi = {10.4230/LIPIcs.WABI.2020.14},
annote = {Keywords: mutation trees, clonal trees, tree distance, phylogenetic trees, tree metric, Robinson - Foulds distance, Bourque distance}
}
Document
Advancing Divide-And-Conquer Phylogeny Estimation Using Robinson-Foulds Supertrees
Abstract
One of the Grand Challenges in Science is the construction of the Tree of Life, an evolutionary tree containing several million species, spanning all life on earth. However, the construction of the Tree of Life is enormously computationally challenging, as all the current most accurate methods are either heuristics for NP-hard optimization problems or Bayesian MCMC methods that sample from tree space. One of the most promising approaches for improving scalability and accuracy for phylogeny estimation uses divide-and-conquer: a set of species is divided into overlapping subsets, trees are constructed on the subsets, and then merged together using a "supertree method". Here, we present Exact-RFS-2, the first polynomial-time algorithm to find an optimal supertree of two trees, using the Robinson-Foulds Supertree (RFS) criterion (a major approach in supertree estimation that is related to maximum likelihood supertrees), and we prove that finding the RFS of three input trees is NP-hard. We also present GreedyRFS (a greedy heuristic that operates by repeatedly using Exact-RFS-2 on pairs of trees, until all the trees are merged into a single supertree). We evaluate Exact-RFS-2 and GreedyRFS, and show that they have better accuracy than the current leading heuristic for RFS.
Cite as
Xilin Yu, Thien Le, Sarah Christensen, Erin K. Molloy, and Tandy Warnow. Advancing Divide-And-Conquer Phylogeny Estimation Using Robinson-Foulds Supertrees. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 15:1-15:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{yu_et_al:LIPIcs.WABI.2020.15,
author = {Yu, Xilin and Le, Thien and Christensen, Sarah and Molloy, Erin K. and Warnow, Tandy},
title = {{Advancing Divide-And-Conquer Phylogeny Estimation Using Robinson-Foulds Supertrees}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {15:1--15:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.15},
URN = {urn:nbn:de:0030-drops-128048},
doi = {10.4230/LIPIcs.WABI.2020.15},
annote = {Keywords: supertrees, divide-and-conquer, phylogeny estimation}
}
Document
Disk Compression of k-mer Sets
Abstract
K-mer based methods have become prevalent in many areas of bioinformatics. In applications such as database search, they often work with large multi-terabyte-sized datasets. Storing such large datasets is a detriment to tool developers, tool users, and reproducibility efforts. General purpose compressors like gzip, or those designed for read data, are sub-optimal because they do not take into account the specific redundancy pattern in k-mer sets. In our earlier work (Rahman and Medvedev, RECOMB 2020), we presented an algorithm UST-Compress that uses a spectrum-preserving string set representation to compress a set of k-mers to disk. In this paper, we present two improved methods for disk compression of k-mer sets, called ESS-Compress and ESS-Tip-Compress. They use a more relaxed notion of string set representation to further remove redundancy from the representation of UST-Compress. We explore their behavior both theoretically and on real data. We show that they improve the compression sizes achieved by UST-Compress by up to 27 percent, across a breadth of datasets. We also derive lower bounds on how well this type of compression strategy can hope to do.
Cite as
Amatur Rahman, Rayan Chikhi, and Paul Medvedev. Disk Compression of k-mer Sets. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 16:1-16:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{rahman_et_al:LIPIcs.WABI.2020.16,
author = {Rahman, Amatur and Chikhi, Rayan and Medvedev, Paul},
title = {{Disk Compression of k-mer Sets}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {16:1--16:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.16},
URN = {urn:nbn:de:0030-drops-128057},
doi = {10.4230/LIPIcs.WABI.2020.16},
annote = {Keywords: de Bruijn graphs, compression, k-mer sets, spectrum-preserving string sets}
}
Document
Near-Linear Time Edit Distance for Indel Channels
Abstract
We consider the following model for sampling pairs of strings: s₁ is a uniformly random bitstring of length n, and s₂ is the bitstring arrived at by applying substitutions, insertions, and deletions to each bit of s₁ with some probability. We show that the edit distance between s₁ and s₂ can be computed in O(n ln n) time with high probability, as long as each bit of s₁ has a mutation applied to it with probability at most a small constant. The algorithm is simple and only uses the textbook dynamic programming algorithm as a primitive, first computing an approximate alignment between the two strings, and then running the dynamic programming algorithm restricted to entries close to the approximate alignment. The analysis of our algorithm provides theoretical justification for alignment heuristics used in practice such as BLAST, FASTA, and MAFFT, which also start by computing approximate alignments quickly and then find the best alignment near the approximate alignment. Our main technical contribution is a partitioning of alignments such that the number of the subsets in the partition is not too large and every alignment in one subset is worse than an alignment considered by our algorithm with high probability. Similar techniques may be of interest in the average-case analysis of other problems commonly solved via dynamic programming.
Cite as
Arun Ganesh and Aaron Sy. Near-Linear Time Edit Distance for Indel Channels. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 17:1-17:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{ganesh_et_al:LIPIcs.WABI.2020.17,
author = {Ganesh, Arun and Sy, Aaron},
title = {{Near-Linear Time Edit Distance for Indel Channels}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {17:1--17:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.17},
URN = {urn:nbn:de:0030-drops-128061},
doi = {10.4230/LIPIcs.WABI.2020.17},
annote = {Keywords: edit distance, average-case analysis, dynamic programming, sequence alignment}
}
Document
Fold Family-Regularized Bayesian Optimization for Directed Protein Evolution
Abstract
Directed Evolution (DE) is a technique for protein engineering that involves iterative rounds of mutagenesis and screening to search for sequences that optimize a given property (ex. binding affinity to a specified target). Unfortunately, the underlying optimization problem is under-determined, and so mutations introduced to improve the specified property may come at the expense of unmeasured, but nevertheless important properties (ex. subcellular localization). We seek to address this issue by incorporating a fold-specific regularization factor into the optimization problem. The regularization factor biases the search towards designs that resemble sequences from the fold family to which the protein belongs. We applied our method to a large library of protein GB1 mutants with binding affinity measurements to IgG-Fc. Our results demonstrate that the regularized optimization problem produces more native-like GB1 sequences with only a minor decrease in binding affinity. Specifically, the log-odds of our designs under a generative model of the GB1 fold family are between 41-45% higher than those obtained without regularization, with only a 7% drop in binding affinity. Thus, our method is capable of making a trade-off between competing traits. Moreover, we demonstrate that our active-learning driven approach reduces the wet-lab burden to identify optimal GB1 designs by 67%, relative to recent results from the Arnold lab on the same data.
Cite as
Trevor S. Frisby and Christopher J. Langmead. Fold Family-Regularized Bayesian Optimization for Directed Protein Evolution. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 18:1-18:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{frisby_et_al:LIPIcs.WABI.2020.18,
author = {Frisby, Trevor S. and Langmead, Christopher J.},
title = {{Fold Family-Regularized Bayesian Optimization for Directed Protein Evolution}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {18:1--18:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.18},
URN = {urn:nbn:de:0030-drops-128077},
doi = {10.4230/LIPIcs.WABI.2020.18},
annote = {Keywords: Protein design, Bayesian Optimization, Gaussian Process Regression, Regularization}
}
Document
Sequence Searching Allowing for Non-Overlapping Adjacent Unbalanced Translocations
Abstract
Unbalanced translocations are among the most frequent chromosomal alterations, accounted for 30% of all losses of heterozygosity, a major genetic event causing inactivation of tumor suppressor genes. Despite of their central role in genomic sequence analysis, little attention has been devoted to the problem of matching sequences allowing for this kind of chromosomal alteration.
In this paper we investigate the approximate string matching problem when the edit operations are non-overlapping unbalanced translocations of adjacent factors. In particular, we first present a 𝒪(nm³)-time and 𝒪(m²)-space algorithm based on the dynamic-programming approach. Then we improve our first result by designing a second solution which makes use of the Directed Acyclic Word Graph of the pattern. In particular, we show that under the assumptions of equiprobability and independence of characters, our algorithm has a 𝒪(nlog²_{σ} m) average time complexity, for an alphabet of size σ, still maintaining the 𝒪(nm³)-time and the 𝒪(m²)-space complexity in the worst case. To the best of our knowledge this is the first solution in literature for the approximate string matching problem allowing for unbalanced translocations of factors.
Cite as
Domenico Cantone, Simone Faro, and Arianna Pavone. Sequence Searching Allowing for Non-Overlapping Adjacent Unbalanced Translocations. In 20th International Workshop on Algorithms in Bioinformatics (WABI 2020). Leibniz International Proceedings in Informatics (LIPIcs), Volume 172, pp. 19:1-19:14, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2020)
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@InProceedings{cantone_et_al:LIPIcs.WABI.2020.19,
author = {Cantone, Domenico and Faro, Simone and Pavone, Arianna},
title = {{Sequence Searching Allowing for Non-Overlapping Adjacent Unbalanced Translocations}},
booktitle = {20th International Workshop on Algorithms in Bioinformatics (WABI 2020)},
pages = {19:1--19:14},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-161-0},
ISSN = {1868-8969},
year = {2020},
volume = {172},
editor = {Kingsford, Carl and Pisanti, Nadia},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2020.19},
URN = {urn:nbn:de:0030-drops-128086},
doi = {10.4230/LIPIcs.WABI.2020.19},
annote = {Keywords: Text processing, approximate matching, inversions, sequence matching}
}