Volume
LIPIcs, Volume 201
21st International Workshop on Algorithms in Bioinformatics (WABI 2021)
-
Part of:
Series:
Leibniz International Proceedings in Informatics (LIPIcs)
Conference: International Workshop on Algorithms in Bioinformatics (WABI)
Event
WABI 2021, August 2-4, 2021, Virtual ConferenceEditors
Publication Details
- published at: 2021-07-22
- Publisher: Schloss Dagstuhl – Leibniz-Zentrum für Informatik
- ISBN: 978-3-95977-200-6
- DBLP: db/conf/wabi/wabi2021
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Document
Complete Volume
LIPIcs, Volume 201, WABI 2021, Complete Volume
Abstract
LIPIcs, Volume 201, WABI 2021, Complete Volume
Cite as
21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 1-400, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@Proceedings{carbone_et_al:LIPIcs.WABI.2021,
title = {{LIPIcs, Volume 201, WABI 2021, Complete Volume}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {1--400},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021},
URN = {urn:nbn:de:0030-drops-143520},
doi = {10.4230/LIPIcs.WABI.2021},
annote = {Keywords: LIPIcs, Volume 201, WABI 2021, Complete Volume}
}
Document
Front Matter
Front Matter, Table of Contents, Preface, Conference Organization
Abstract
Front Matter, Table of Contents, Preface, Conference Organization
Cite as
21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 0:i-0:x, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{carbone_et_al:LIPIcs.WABI.2021.0,
author = {Carbone, Alessandra and El-Kebir, Mohammed},
title = {{Front Matter, Table of Contents, Preface, Conference Organization}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {0:i--0:x},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.0},
URN = {urn:nbn:de:0030-drops-143531},
doi = {10.4230/LIPIcs.WABI.2021.0},
annote = {Keywords: Front Matter, Table of Contents, Preface, Conference Organization}
}
Document
The Most Parsimonious Reconciliation Problem in the Presence of Incomplete Lineage Sorting and Hybridization Is NP-Hard
Abstract
The maximum parsimony phylogenetic reconciliation problem seeks to explain incongruity between a gene phylogeny and a species phylogeny with respect to a set of evolutionary events. While the reconciliation problem is well-studied for species and gene trees subject to events such as duplication, transfer, loss, and deep coalescence, recent work has examined species phylogenies that incorporate hybridization and are thus represented by networks rather than trees. In this paper, we show that the problem of computing a maximum parsimony reconciliation for a gene tree and species network is NP-hard even when only considering deep coalescence. This result suggests that future work on maximum parsimony reconciliation for species networks should explore approximation algorithms and heuristics.
Cite as
Matthew LeMay, Yi-Chieh Wu, and Ran Libeskind-Hadas. The Most Parsimonious Reconciliation Problem in the Presence of Incomplete Lineage Sorting and Hybridization Is NP-Hard. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 1:1-1:10, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{lemay_et_al:LIPIcs.WABI.2021.1,
author = {LeMay, Matthew and Wu, Yi-Chieh and Libeskind-Hadas, Ran},
title = {{The Most Parsimonious Reconciliation Problem in the Presence of Incomplete Lineage Sorting and Hybridization Is NP-Hard}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {1:1--1:10},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.1},
URN = {urn:nbn:de:0030-drops-143546},
doi = {10.4230/LIPIcs.WABI.2021.1},
annote = {Keywords: phylogenetics, reconciliation, deep coalescence, hybridization, NP-hardness}
}
Document
Efficient Privacy-Preserving Variable-Length Substring Match for Genome Sequence
Abstract
Finding a similar substring that commonly appears in query and database sequences is an essential task for genome data analysis. This study proposes a secure two-party variable-length string search protocol based on secret sharing. The unique feature of our protocol is that time, communication, and round complexities are not dependent on the database length N, after the query input. This property brings dramatic performance improvements in search time, since N is usually quite large in an actual genome database, and the same database is repeatedly used for many queries. Our concept hinges on a technique that efficiently applies the compressed full-text index (FOCS 2000) for a secret-sharing scheme. We conducted an experiment using a human genomic sequence with the length of 10 million as the database and a query with the length of 100 and found that the query response time of our protocol was at least three orders of magnitude faster than a well-designed baseline protocol under the realistic computation/network environment.
Cite as
Yoshiki Nakagawa, Satsuya Ohata, and Kana Shimizu. Efficient Privacy-Preserving Variable-Length Substring Match for Genome Sequence. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 2:1-2:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{nakagawa_et_al:LIPIcs.WABI.2021.2,
author = {Nakagawa, Yoshiki and Ohata, Satsuya and Shimizu, Kana},
title = {{Efficient Privacy-Preserving Variable-Length Substring Match for Genome Sequence}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {2:1--2:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.2},
URN = {urn:nbn:de:0030-drops-143552},
doi = {10.4230/LIPIcs.WABI.2021.2},
annote = {Keywords: Private Genome Sequence Search, Secure Multiparty Computation, Secret Sharing, FM-index, Suffix Tree, Maximal Exact Match}
}
Document
Making Sense of a Cophylogeny Output: Efficient Listing of Representative Reconciliations
Abstract
Cophylogeny reconciliation is a powerful method for analyzing host-parasite (or host-symbiont) co-evolution. It models co-evolution as an optimization problem where the set of all optimal solutions may represent different biological scenarios which thus need to be analyzed separately. Despite the significant research done in the area, few approaches have addressed the problem of helping the biologist deal with the often huge space of optimal solutions. In this paper, we propose a new approach to tackle this problem. We introduce three different criteria under which two solutions may be considered biologically equivalent, and then we propose polynomial-delay algorithms that enumerate only one representative per equivalence class (without listing all the solutions). Our results are of both theoretical and practical importance. Indeed, as shown by the experiments, we are able to significantly reduce the space of optimal solutions while still maintaining important biological information about the whole space.
Cite as
Yishu Wang, Arnaud Mary, Marie-France Sagot, and Blerina Sinaimeri. Making Sense of a Cophylogeny Output: Efficient Listing of Representative Reconciliations. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 3:1-3:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{wang_et_al:LIPIcs.WABI.2021.3,
author = {Wang, Yishu and Mary, Arnaud and Sagot, Marie-France and Sinaimeri, Blerina},
title = {{Making Sense of a Cophylogeny Output: Efficient Listing of Representative Reconciliations}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {3:1--3:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.3},
URN = {urn:nbn:de:0030-drops-143564},
doi = {10.4230/LIPIcs.WABI.2021.3},
annote = {Keywords: Cophylogeny, Enumeration, Equivalence relation, Dynamic programming}
}
Document
Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth
Abstract
There has been rapid development of probabilistic models and inference methods for transcript abundance estimation from RNA-seq data. These models aim to accurately estimate transcript-level abundances, to account for different biases in the measurement process, and even to assess uncertainty in resulting estimates that can be propagated to subsequent analyses. The assumed accuracy of the estimates inferred by such methods underpin gene expression based analysis routinely carried out in the lab. Although hyperparameter selection is known to affect the distributions of inferred abundances (e.g. producing smooth versus sparse estimates), strategies for performing model selection in experimental data have been addressed informally at best.
Thus, we derive perplexity for evaluating abundance estimates on fragment sets directly. We adapt perplexity from the analogous metric used to evaluate language and topic models and extend the metric to carefully account for corner cases unique to RNA-seq. In experimental data, estimates with the best perplexity also best correlate with qPCR measurements. In simulated data, perplexity is well behaved and concordant with genome-wide measurements against ground truth and differential expression analysis.
To our knowledge, our study is the first to make possible model selection for transcript abundance estimation on experimental data in the absence of ground truth.
Cite as
Jason Fan, Skylar Chan, and Rob Patro. Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 4:1-4:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{fan_et_al:LIPIcs.WABI.2021.4,
author = {Fan, Jason and Chan, Skylar and Patro, Rob},
title = {{Perplexity: Evaluating Transcript Abundance Estimation in the Absence of Ground Truth}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {4:1--4:22},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.4},
URN = {urn:nbn:de:0030-drops-143578},
doi = {10.4230/LIPIcs.WABI.2021.4},
annote = {Keywords: RNA-seq, transcript abundance estimation, model selection}
}
Document
The Maximum Duo-Preservation String Mapping Problem with Bounded Alphabet
Abstract
Given two strings A and B such that B is a permutation of A, the max duo-preservation string mapping (MPSM) problem asks to find a mapping π between them so as to preserve a maximum number of duos. A duo is any pair of consecutive characters in a string and it is preserved by π if its two consecutive characters in A are mapped to same two consecutive characters in B. This problem has received a growing attention in recent years, partly as an alternative way to produce approximation algorithms for its minimization counterpart, min common string partition, a widely studied problem due its applications in comparative genomics. Considering this favored field of application with short alphabet, it is surprising that MPSM^𝓁, the variant of MPSM with bounded alphabet, has received so little attention, with a single yet impressive work that provides a 2.67-approximation achieved in O(n) [Brubach, 2018], where n = |A| = |B|. Our work focuses on MPSM^𝓁, and our main contribution is the demonstration that this problem admits a Polynomial Time Approximation Scheme (PTAS) when 𝓁 = O(1). We also provide an alternate, somewhat simpler, proof of NP-hardness for this problem compared with the NP-hardness proof presented in [Haitao Jiang et al., 2012].
Cite as
Nicolas Boria, Laurent Gourvès, Vangelis Th. Paschos, and Jérôme Monnot. The Maximum Duo-Preservation String Mapping Problem with Bounded Alphabet. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 5:1-5:12, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{boria_et_al:LIPIcs.WABI.2021.5,
author = {Boria, Nicolas and Gourv\`{e}s, Laurent and Paschos, Vangelis Th. and Monnot, J\'{e}r\^{o}me},
title = {{The Maximum Duo-Preservation String Mapping Problem with Bounded Alphabet}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {5:1--5:12},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.5},
URN = {urn:nbn:de:0030-drops-143586},
doi = {10.4230/LIPIcs.WABI.2021.5},
annote = {Keywords: Maximum-Duo Preservation String Mapping, Bounded alphabet, Polynomial Time Approximation Scheme}
}
Document
Treewidth-Based Algorithms for the Small Parsimony Problem on Networks
Abstract
Phylogenetic reconstruction is one of the paramount challenges of contemporary bioinformatics. A subtask of existing tree reconstruction algorithms is modeled by the Small Parsimony problem: given a tree T and an assignment of character-states to its leaves, assign states to the internal nodes of T such as to minimize the parsimony score, that is, the number of edges of T connecting nodes with different states. While this problem is polynomial-time solvable on trees, the matter is more complicated if T contains reticulate events such as hybridizations or recombinations, i.e. when T is a network. Indeed, three different versions of the parsimony score on networks have been proposed and each of them is NP-hard to decide. Existing parameterized algorithms focus on combining the number of possible character-states with the number of reticulate events (per biconnected component). Here, we consider the treewidth of the undirected graph underlying the input network as parameter, presenting dynamic programming algorithms for (slight generalizations of) all three versions of the parsimony problem on networks. Our algorithms use a formulation of the treewidth that may facilitate formalizing treewidth-based dynamic programming algorithms on phylogenetic networks for other problems.
Cite as
Celine Scornavacca and Mathias Weller. Treewidth-Based Algorithms for the Small Parsimony Problem on Networks. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 6:1-6:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{scornavacca_et_al:LIPIcs.WABI.2021.6,
author = {Scornavacca, Celine and Weller, Mathias},
title = {{Treewidth-Based Algorithms for the Small Parsimony Problem on Networks}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {6:1--6:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.6},
URN = {urn:nbn:de:0030-drops-143591},
doi = {10.4230/LIPIcs.WABI.2021.6},
annote = {Keywords: Phylogenetics, parsimony, phylogenetic networks, parameterized complexity, dynamic programming, treewidth}
}
Document
Tree Diet: Reducing the Treewidth to Unlock FPT Algorithms in RNA Bioinformatics
Abstract
Hard graph problems are ubiquitous in Bioinformatics, inspiring the design of specialized Fixed-Parameter Tractable algorithms, many of which rely on a combination of tree-decomposition and dynamic programming. The time/space complexities of such approaches hinge critically on low values for the treewidth tw of the input graph. In order to extend their scope of applicability, we introduce the Tree-Diet problem, i.e. the removal of a minimal set of edges such that a given tree-decomposition can be slimmed down to a prescribed treewidth tw'. Our rationale is that the time gained thanks to a smaller treewidth in a parameterized algorithm compensates the extra post-processing needed to take deleted edges into account.
Our core result is an FPT dynamic programming algorithm for Tree-Diet, using 2^{O(tw)}n time and space. We complement this result with parameterized complexity lower-bounds for stronger variants (e.g., NP-hardness when tw' or tw-tw' is constant). We propose a prototype implementation for our approach which we apply on difficult instances of selected RNA-based problems: RNA design, sequence-structure alignment, and search of pseudoknotted RNAs in genomes, revealing very encouraging results. This work paves the way for a wider adoption of tree-decomposition-based algorithms in Bioinformatics.
Cite as
Bertrand Marchand, Yann Ponty, and Laurent Bulteau. Tree Diet: Reducing the Treewidth to Unlock FPT Algorithms in RNA Bioinformatics. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 7:1-7:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{marchand_et_al:LIPIcs.WABI.2021.7,
author = {Marchand, Bertrand and Ponty, Yann and Bulteau, Laurent},
title = {{Tree Diet: Reducing the Treewidth to Unlock FPT Algorithms in RNA Bioinformatics}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {7:1--7:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.7},
URN = {urn:nbn:de:0030-drops-143604},
doi = {10.4230/LIPIcs.WABI.2021.7},
annote = {Keywords: RNA, treewidth, FPT algorithms, RNA design, structure-sequence alignment}
}
Document
Space-Efficient Representation of Genomic k-Mer Count Tables
Abstract
Motivation. k-mer counting is a common task in bioinformatic pipelines, with many dedicated tools available. Output formats could rely on quotienting to reduce the space of k-mers in hash tables, however counts are not usually stored in space-efficient formats. Overall, k-mer count tables for genomic data take a considerable space, easily reaching tens of GB. Furthermore, such tables do not support efficient random-access queries in general.
Results. In this work, we design an efficient representation of k-mer count tables supporting fast random-access queries. We propose to apply Compressed Static Functions (CSFs), with space proportional to the empirical zero-order entropy of the counts. For very skewed distributions, like those of k-mer counts in whole genomes, the only currently available implementation of CSFs does not provide a compact enough representation. By adding a Bloom Filter to a CSF we obtain a Bloom-enhanced CSF (BCSF) effectively overcoming this limitation. Furthermore, by combining BCSFs with minimizer-based bucketing of k-mers, we build even smaller representations breaking the empirical entropy lower bound, for large enough k. We also extend these representations to the approximate case, gaining additional space. We experimentally validate these techniques on k-mer count tables of whole genomes (E.Coli and C.Elegans) as well as on k-mer document frequency tables for 29 E.Coli genomes. In the case of exact counts, our representation takes about a half of the space of the empirical entropy, for large enough k’s.
Cite as
Yoshihiro Shibuya, Djamal Belazzougui, and Gregory Kucherov. Space-Efficient Representation of Genomic k-Mer Count Tables. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 8:1-8:19, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{shibuya_et_al:LIPIcs.WABI.2021.8,
author = {Shibuya, Yoshihiro and Belazzougui, Djamal and Kucherov, Gregory},
title = {{Space-Efficient Representation of Genomic k-Mer Count Tables}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {8:1--8:19},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.8},
URN = {urn:nbn:de:0030-drops-143619},
doi = {10.4230/LIPIcs.WABI.2021.8},
annote = {Keywords: k-mer counting, data structures, compression, minimizers, compressed static function, Bloom filter, empirical entropy}
}
Document
Parsimonious Clone Tree Reconciliation in Cancer
Abstract
Every tumor is composed of heterogeneous clones, each corresponding to a distinct subpopulation of cells that accumulated different types of somatic mutations, ranging from single-nucleotide variants (SNVs) to copy-number aberrations (CNAs). As the analysis of this intra-tumor heterogeneity has important clinical applications, several computational methods have been introduced to identify clones from DNA sequencing data. However, due to technological and methodological limitations, current analyses are restricted to identifying tumor clones only based on either SNVs or CNAs, preventing a comprehensive characterization of a tumor’s clonal composition. To overcome these challenges, we formulate the identification of clones in terms of both SNVs and CNAs as a reconciliation problem while accounting for uncertainty in the input SNV and CNA proportions. We thus characterize the computational complexity of this problem and we introduce a mixed integer linear programming formulation to solve it exactly. On simulated data, we show that tumor clones can be identified reliably, especially when further taking into account the ancestral relationships that can be inferred from the input SNVs and CNAs. On 49 tumor samples from 10 prostate cancer patients, our reconciliation approach provides a higher resolution view of tumor evolution than previous studies.
Cite as
Palash Sashittal, Simone Zaccaria, and Mohammed El-Kebir. Parsimonious Clone Tree Reconciliation in Cancer. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 9:1-9:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{sashittal_et_al:LIPIcs.WABI.2021.9,
author = {Sashittal, Palash and Zaccaria, Simone and El-Kebir, Mohammed},
title = {{Parsimonious Clone Tree Reconciliation in Cancer}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {9:1--9:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.9},
URN = {urn:nbn:de:0030-drops-143624},
doi = {10.4230/LIPIcs.WABI.2021.9},
annote = {Keywords: Intra-tumor heterogeneity, phylogenetics, mixed integer linear programming}
}
Document
An Efficient Linear Mixed Model Framework for Meta-Analytic Association Studies Across Multiple Contexts
Abstract
Linear mixed models (LMMs) can be applied in the meta-analyses of responses from individuals across multiple contexts, increasing power to detect associations while accounting for confounding effects arising from within-individual variation. However, traditional approaches to fitting these models can be computationally intractable. Here, we describe an efficient and exact method for fitting a multiple-context linear mixed model. Whereas existing exact methods may be cubic in their time complexity with respect to the number of individuals, our approach for multiple-context LMMs (mcLMM) is linear. These improvements allow for large-scale analyses requiring computing time and memory magnitudes of order less than existing methods. As examples, we apply our approach to identify expression quantitative trait loci from large-scale gene expression data measured across multiple tissues as well as joint analyses of multiple phenotypes in genome-wide association studies at biobank scale.
Cite as
Brandon Jew, Jiajin Li, Sriram Sankararaman, and Jae Hoon Sul. An Efficient Linear Mixed Model Framework for Meta-Analytic Association Studies Across Multiple Contexts. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 10:1-10:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{jew_et_al:LIPIcs.WABI.2021.10,
author = {Jew, Brandon and Li, Jiajin and Sankararaman, Sriram and Sul, Jae Hoon},
title = {{An Efficient Linear Mixed Model Framework for Meta-Analytic Association Studies Across Multiple Contexts}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {10:1--10:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.10},
URN = {urn:nbn:de:0030-drops-143632},
doi = {10.4230/LIPIcs.WABI.2021.10},
annote = {Keywords: Meta-analysis, Linear mixed models, multiple-context genetic association}
}
Document
LRBinner: Binning Long Reads in Metagenomics Datasets
Abstract
Advancements in metagenomics sequencing allow the study of microbial communities directly from their environments. Metagenomics binning is a key step in the species characterisation of microbial communities. Next-generation sequencing reads are usually assembled into contigs for metagenomics binning mainly due to the limited information within short reads. Third-generation sequencing provides much longer reads that have lengths similar to the contigs assembled from short reads. However, existing contig-binning tools cannot be directly applied on long reads due to the absence of coverage information and the presence of high error rates. The few existing long-read binning tools either use only composition or use composition and coverage information separately. This may ignore bins that correspond to low-abundance species or erroneously split bins that correspond to species with non-uniform coverages. Here we present a reference-free binning approach, LRBinner, that combines composition and coverage information of complete long-read datasets. LRBinner also uses a distance-histogram-based clustering algorithm to extract clusters with varying sizes. The experimental results on both simulated and real datasets show that LRBinner achieves the best binning accuracy against the baselines. Moreover, we show that binning reads using LRBinner prior to assembly reduces computational resources for assembly while attaining satisfactory assembly qualities.
Cite as
Anuradha Wickramarachchi and Yu Lin. LRBinner: Binning Long Reads in Metagenomics Datasets. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 11:1-11:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{wickramarachchi_et_al:LIPIcs.WABI.2021.11,
author = {Wickramarachchi, Anuradha and Lin, Yu},
title = {{LRBinner: Binning Long Reads in Metagenomics Datasets}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {11:1--11:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.11},
URN = {urn:nbn:de:0030-drops-143644},
doi = {10.4230/LIPIcs.WABI.2021.11},
annote = {Keywords: Metagenomics binning, long reads, machine learning, clustering}
}
Document
Compression of Multiple k-Mer Sets by Iterative SPSS Decomposition
Abstract
A set of k-mers is used in many bioinformatics tasks, and much work has been done on methods to efficiently represent or compress a single set of k-mers. However, methods for compressing multiple k-mer sets have been less studied in spite of their obvious benefits for researchers and genome-related database maintainers. This paper proposes an algorithm to compress multiple k-mer sets, which works by iteratively splitting SPSS (spectrum-preserving string sets). In experiments with 3292 k-mer sets constructed from E. coli whole-genome sequencing data and 2555 k-mer sets constructed from human RNA-Seq data, the proposed algorithm could reduce the compressed file sizes by 34.7% and 13.2% respectively compared to one of the state-of-the-art colored de Bruijn graph representations. Also, our method used less memory than the colored de Bruijn graph method. This paper also introduces various methods to make the compression algorithm efficient in terms of time and memory, one of which is a parallelizable small-weight SPSS construction algorithm.
Cite as
Kazushi Kitaya and Tetsuo Shibuya. Compression of Multiple k-Mer Sets by Iterative SPSS Decomposition. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 12:1-12:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{kitaya_et_al:LIPIcs.WABI.2021.12,
author = {Kitaya, Kazushi and Shibuya, Tetsuo},
title = {{Compression of Multiple k-Mer Sets by Iterative SPSS Decomposition}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {12:1--12:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.12},
URN = {urn:nbn:de:0030-drops-143659},
doi = {10.4230/LIPIcs.WABI.2021.12},
annote = {Keywords: sequencing data, k-mer, de Bruijn graph, compression, colored de Bruijn graph}
}
Document
Compressing and Indexing Aligned Readsets
Abstract
Compressed full-text indexes are one of the main success stories of bioinformatics data structures but even they struggle to handle some DNA readsets. This may seem surprising since, at least when dealing with short reads from the same individual, the readset will be highly repetitive and, thus, highly compressible. If we are not careful, however, this advantage can be more than offset by two disadvantages: first, since most base pairs are included in at least tens reads each, the uncompressed readset is likely to be at least an order of magnitude larger than the individual’s uncompressed genome; second, these indexes usually pay some space overhead for each string they store, and the total overhead can be substantial when dealing with millions of reads.
The most successful compressed full-text indexes for readsets so far are based on the Extended Burrows-Wheeler Transform (EBWT) and use a sorting heuristic to try to reduce the space overhead per read, but they still treat the reads as separate strings and thus may not take full advantage of the readset’s structure. For example, if we have already assembled an individual’s genome from the readset, then we can usually use it to compress the readset well: e.g., we store the gap-coded list of reads' starting positions; we store the list of their lengths, which is often highly compressible; and we store information about the sequencing errors, which are rare with short reads. There is nowhere, however, where we can plug an assembled genome into the EBWT.
In this paper we show how to use one or more assembled or partially assembled genome as the basis for a compressed full-text index of its readset. Specifically, we build a labelled tree by taking the assembled genome as a trunk and grafting onto it the reads that align to it, at the starting positions of their alignments. Next, we compute the eXtended Burrows-Wheeler Transform (XBWT) of the resulting labelled tree and build a compressed full-text index on that. Although this index can occasionally return false positives, it is usually much more compact than the alternatives. Following the established practice for datasets with many repetitions, we compare different full-text indices by looking at the number of runs in the transformed strings. For a human Chr19 readset our preliminary experiments show that eliminating separators characters from the EBWT reduces the number of runs by 19%, from 220 million to 178 million, and using the XBWT reduces it by a further 15%, to 150 million.
Cite as
Travis Gagie, Garance Gourdel, and Giovanni Manzini. Compressing and Indexing Aligned Readsets. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 13:1-13:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{gagie_et_al:LIPIcs.WABI.2021.13,
author = {Gagie, Travis and Gourdel, Garance and Manzini, Giovanni},
title = {{Compressing and Indexing Aligned Readsets}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {13:1--13:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.13},
URN = {urn:nbn:de:0030-drops-143660},
doi = {10.4230/LIPIcs.WABI.2021.13},
annote = {Keywords: data compression, compact data structures, FM-index, Burrows-Wheeler Transform, EBWT, XBWT, DNA reads}
}
Document
BPPart: RNA-RNA Interaction Partition Function in the Absence of Entropy
Abstract
A few classes of RNA-RNA interaction (RRI) with complex roles in cellular functions, such as miRNA-target and lncRNAs, have already been studied. Accordingly, RRI bioinformatics tools proposed in the last decade are tailored for those specific classes. Interestingly, there are somewhat unnoticed mRNA-mRNA interactions in the literature with potentially drastic biological roles. Hence, there is a need for high-throughput generic RRI bioinformatics tools that can be used in more comprehensive settings. In this work, we revisit two of the RRI partition function algorithms, piRNA and rip. These are equivalent methods that implement the most comprehensive and computationally intensive thermodynamic model for RRI. We propose simpler models that are shown to retain the vast majority of the thermodynamic information that the more complex models capture. Specifically, we simplify the energy model by ignoring the system’s entropy and show its equivalency to a base-pair counting model. We allow different weights for base-pairs to maximize the correlations with the full thermodynamic model. Our newly developed algorithm, BPPart, is 225× faster than piRNA and is more expressive and easier to analyze due to its simplicity and order of magnitude reduction in the number of dynamic programming tables. Still, based on our analysis of both the real and randomly generated data, its scores achieve a correlation of 0.855 with piRNA at 37^{∘}C. Finally, we illustrate one use-case of such simpler models to generate hypotheses about the roles of specific RNAs in various diseases. We have made our tool publicly available and believe that this faster and more expressive model will make the incorporation of physics-guided information in complex RRI analysis and prediction models more accessible.
Cite as
Ali Ebrahimpour-Boroojeny, Sanjay Rajopadhye, and Hamidreza Chitsaz. BPPart: RNA-RNA Interaction Partition Function in the Absence of Entropy. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 14:1-14:24, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{ebrahimpourboroojeny_et_al:LIPIcs.WABI.2021.14,
author = {Ebrahimpour-Boroojeny, Ali and Rajopadhye, Sanjay and Chitsaz, Hamidreza},
title = {{BPPart: RNA-RNA Interaction Partition Function in the Absence of Entropy}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {14:1--14:24},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.14},
URN = {urn:nbn:de:0030-drops-143673},
doi = {10.4230/LIPIcs.WABI.2021.14},
annote = {Keywords: RNA-RNA Interaction, Partition Function, RNA Secondary Structure}
}
Document
BISER: Fast Characterization of Segmental Duplication Structure in Multiple Genome Assemblies
Abstract
The increasing availability of high-quality genome assemblies raised interest in the characterization of genomic architecture. Major architectural parts, such as common repeats and segmental duplications (SDs), increase genome plasticity that stimulates further evolution by changing the genomic structure. However, optimal computation of SDs through standard local alignment algorithms is impractical due to the size of most genomes. A cross-genome evolutionary analysis of SDs is even harder, as one needs to characterize SDs in multiple genomes and find relations between those SDs and unique segments in other genomes. Thus there is a need for fast and accurate algorithms to characterize SD structure in multiple genome assemblies to better understand the evolutionary forces that shaped the genomes of today.
Here we introduce a new tool, BISER, to quickly detect SDs in multiple genomes and identify elementary SDs and core duplicons that drive the formation of such SDs. BISER improves earlier tools by (i) scaling the detection of SDs with low homology (75%) to multiple genomes while introducing further 8-24x speed-ups over the existing tools, and by (ii) characterizing elementary SDs and detecting core duplicons to help trace the evolutionary history of duplications to as far as 90 million years.
Cite as
Hamza Išerić, Can Alkan, Faraz Hach, and Ibrahim Numanagić. BISER: Fast Characterization of Segmental Duplication Structure in Multiple Genome Assemblies. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 15:1-15:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{iseric_et_al:LIPIcs.WABI.2021.15,
author = {I\v{s}eri\'{c}, Hamza and Alkan, Can and Hach, Faraz and Numanagi\'{c}, Ibrahim},
title = {{BISER: Fast Characterization of Segmental Duplication Structure in Multiple Genome Assemblies}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {15:1--15:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.15},
URN = {urn:nbn:de:0030-drops-143681},
doi = {10.4230/LIPIcs.WABI.2021.15},
annote = {Keywords: genome analysis, fast alignment, segmental duplications, core duplicons, sequence decomposition}
}
Document
Flow Decomposition with Subpath Constraints
Abstract
Flow network decomposition is a natural model for problems where we are given a flow network arising from superimposing a set of weighted paths and would like to recover the underlying data, i.e., decompose the flow into the original paths and their weights. Thus, variations on flow decomposition are often used as subroutines in multiassembly problems such as RNA transcript assembly. In practice, we frequently have access to information beyond flow values in the form of subpaths, and many tools incorporate these heuristically. But despite acknowledging their utility in practice, previous work has not formally addressed the effect of subpath constraints on the accuracy of flow network decomposition approaches. We formalize the flow decomposition with subpath constraints problem, give the first algorithms for it, and study its usefulness for recovering ground truth decompositions. For finding a minimum decomposition, we propose both a heuristic and an FPT algorithm. Experiments on RNA transcript datasets show that for instances with larger solution path sets, the addition of subpath constraints finds 13% more ground truth solutions when minimal decompositions are found exactly, and 30% more ground truth solutions when minimal decompositions are found heuristically.
Cite as
Lucia Williams, Alexandru I. Tomescu, and Brendan Mumey. Flow Decomposition with Subpath Constraints. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 16:1-16:15, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{williams_et_al:LIPIcs.WABI.2021.16,
author = {Williams, Lucia and Tomescu, Alexandru I. and Mumey, Brendan},
title = {{Flow Decomposition with Subpath Constraints}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {16:1--16:15},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.16},
URN = {urn:nbn:de:0030-drops-143695},
doi = {10.4230/LIPIcs.WABI.2021.16},
annote = {Keywords: Flow decomposition, subpath constraints, RNA-Seq}
}
Document
Conflict Resolution Algorithms for Deep Coalescence Phylogenetic Networks
Abstract
We address the problem of inferring an optimal tree displayed by a network, given a gene tree G and a tree-child network N, under the deep coalescence cost. We propose an O(|G||N|)-time dynamic programming algorithm (DP) to compute a lower bound of the optimal displayed tree cost, where |G| and |N| are the sizes of G and N, respectively. This algorithm has the ability to state whether the cost is exact or is a lower bound. In addition, our algorithm provides a set of reticulation edges that correspond to the obtained cost. If the cost is exact, the set induces an optimal displayed tree that yields the cost. If the cost is a lower bound, the set contains pairs of conflicting edges, that is, edges sharing a reticulation node. Next, we show a conflict resolution algorithm that requires 2^{r+1}-1 invocations of DP in the worst case, where r is a number of reticulations. We propose a similar O(2^k|G||N|)-time algorithm for level-k networks and a branch and bound solution to compute lower and upper bounds of optimal costs. We also show how our algorithms can be extended to a broader class of phylogenetic networks. Despite their exponential complexity in the worst case, our solutions perform significantly well on empirical and simulated datasets, thanks to the strategy of resolving internal dissimilarities between gene trees and networks. In particular, experiments on simulated data indicate that the runtime of our solution is Θ(2^{0.543 k}|G||N|) on average. Therefore, our solution is an efficient alternative to enumeration strategies commonly proposed in the literature and enables analyses of complex networks with dozens of reticulations.
Cite as
Marcin Wawerka, Dawid Dąbkowski, Natalia Rutecka, Agnieszka Mykowiecka, and Paweł Górecki. Conflict Resolution Algorithms for Deep Coalescence Phylogenetic Networks. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 17:1-17:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{wawerka_et_al:LIPIcs.WABI.2021.17,
author = {Wawerka, Marcin and D\k{a}bkowski, Dawid and Rutecka, Natalia and Mykowiecka, Agnieszka and G\'{o}recki, Pawe{\l}},
title = {{Conflict Resolution Algorithms for Deep Coalescence Phylogenetic Networks}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {17:1--17:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.17},
URN = {urn:nbn:de:0030-drops-143708},
doi = {10.4230/LIPIcs.WABI.2021.17},
annote = {Keywords: Phylogenetic Network, Gene Tree, Species Tree, Deep Coalescence, Reticulation, Optimal Displayed Tree}
}
Document
Genome Halving and Aliquoting Under the Copy Number Distance
Abstract
Large-scale genome rearrangements occur frequently in species evolution and cancer evolution. While the computation of evolutionary distances is tractable for balanced rearrangements, such as inversions and translocations, computing distances involving duplications and deletions is much more difficult. In the recently proposed Copy Number Distance (CND) model, a genome is represented as a Copy Number Profile (CNP), a sequence of integers, and the CND between two CNPs is the length of a shortest sequence of deletions and amplifications of contiguous segments that transforms one CNP into the other. In addition to these segmental events, genomes also undergo global events such as Whole Genome Duplication (WGD) or polyploidization that multiply the entire genome content. These global events are common and important in both species and cancer evolution. In this paper, we formulate the genome halving problem of finding a closest preduplication CNP that has undergone a WGD and evolved into a given CNP under the CND model. We also formulate the analogous genome aliquoting problem of finding the closest prepolyploidzation CNP under the CND distance. We give a linear time algorithm for the halving distance and a quadratic time dynamic programming algorithm for the aliquoting distance. We implement these algorithms and show that they produce reasonable solutions on simulated CNPs.
Cite as
Ron Zeira, Geoffrey Mon, and Benjamin J. Raphael. Genome Halving and Aliquoting Under the Copy Number Distance. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 18:1-18:25, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{zeira_et_al:LIPIcs.WABI.2021.18,
author = {Zeira, Ron and Mon, Geoffrey and Raphael, Benjamin J.},
title = {{Genome Halving and Aliquoting Under the Copy Number Distance}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {18:1--18:25},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.18},
URN = {urn:nbn:de:0030-drops-143711},
doi = {10.4230/LIPIcs.WABI.2021.18},
annote = {Keywords: Genome rearrangements, Copy number distance, Whole genome duplication, polyploidization, genome halving distance, genome aliquoting distance}
}
Document
Efficient Haplotype Block Matching in Bi-Directional PBWT
Abstract
Efficient haplotype matching search is of great interest when large genotyped cohorts are becoming available. Positional Burrows-Wheeler Transform (PBWT) enables efficient searching for blocks of haplotype matches. However, existing efficient PBWT algorithms sweep across the haplotype panel from left to right, capturing all exact matches. As a result, PBWT does not account for mismatches. It is also not easy to investigate the patterns of changes between the matching blocks. Here, we present an extension to PBWT, called bi-directional PBWT that allows the information about the blocks of matches to be present at both sides of each site. We also present a set of algorithms to efficiently merge the matching blocks or examine the patterns of changes on both sides of each site. The time complexity of the algorithms to find and merge matching blocks using bi-directional PBWT is linear to the input size.
Using real data from the UK Biobank, we demonstrate the run time and memory efficiency of our algorithms. More importantly, our algorithms can identify more blocks by enabling tolerance of mismatches. Moreover, by using mutual information (MI) between the forward and the reverse PBWT matching block sets as a measure of haplotype consistency, we found the MI derived from European samples in the 1000 Genomes Project is highly correlated (Spearman correlation r=0.87) with the deCODE recombination map.
Cite as
Ardalan Naseri, William Yue, Shaojie Zhang, and Degui Zhi. Efficient Haplotype Block Matching in Bi-Directional PBWT. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 19:1-19:13, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{naseri_et_al:LIPIcs.WABI.2021.19,
author = {Naseri, Ardalan and Yue, William and Zhang, Shaojie and Zhi, Degui},
title = {{Efficient Haplotype Block Matching in Bi-Directional PBWT}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {19:1--19:13},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.19},
URN = {urn:nbn:de:0030-drops-143729},
doi = {10.4230/LIPIcs.WABI.2021.19},
annote = {Keywords: PBWT, Bi-directional, Haplotype Matching}
}
Document
Fast Approximate Shortest Hyperpaths for Inferring Pathways in Cell Signaling Hypergraphs
Abstract
Cell signaling pathways, which are a series of reactions that start at receptors and end at transcription factors, are basic to systems biology. Properly modeling the reactions in such pathways requires directed hypergraphs, where an edge is now directed between two sets of vertices. Inferring a pathway by the most parsimonious series of reactions then corresponds to finding a shortest hyperpath in a directed hypergraph, which is NP-complete. The state of the art for shortest hyperpaths in cell-signaling hypergraphs solves a mixed-integer linear program to find an optimal hyperpath that is restricted to be acyclic, and offers no efficiency guarantees.
We present for the first time a heuristic for general shortest hyperpaths that properly handles cycles, and is guaranteed to be efficient. Its accuracy is demonstrated through exhaustive experiments on all instances from the standard NCI-PID and Reactome pathway databases, which show the heuristic finds a hyperpath that matches the state-of-the-art mixed-integer linear program on over 99% of all instances that are acyclic. On instances where only cyclic hyperpaths exist, the heuristic surpasses the state-of-the-art, which finds no solution; on every such cyclic instance, enumerating all possible hyperpaths shows that the solution found by the heuristic is in fact optimal.
Cite as
Spencer Krieger and John Kececioglu. Fast Approximate Shortest Hyperpaths for Inferring Pathways in Cell Signaling Hypergraphs. In 21st International Workshop on Algorithms in Bioinformatics (WABI 2021). Leibniz International Proceedings in Informatics (LIPIcs), Volume 201, pp. 20:1-20:20, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2021)
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@InProceedings{krieger_et_al:LIPIcs.WABI.2021.20,
author = {Krieger, Spencer and Kececioglu, John},
title = {{Fast Approximate Shortest Hyperpaths for Inferring Pathways in Cell Signaling Hypergraphs}},
booktitle = {21st International Workshop on Algorithms in Bioinformatics (WABI 2021)},
pages = {20:1--20:20},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-200-6},
ISSN = {1868-8969},
year = {2021},
volume = {201},
editor = {Carbone, Alessandra and El-Kebir, Mohammed},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops-dev.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2021.20},
URN = {urn:nbn:de:0030-drops-143733},
doi = {10.4230/LIPIcs.WABI.2021.20},
annote = {Keywords: Systems biology, cell signaling networks, reaction pathways, directed hypergraphs, shortest hyperpaths, efficient heuristics, hyperpath enumeration}
}