Volume
LIPIcs, Volume 312
24th International Workshop on Algorithms in Bioinformatics (WABI 2024)
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Leibniz International Proceedings in Informatics (LIPIcs)
Conference: International Workshop on Algorithms in Bioinformatics (WABI)
Publication Details
- published at: 2024-08-26
- Publisher: Schloss Dagstuhl – Leibniz-Zentrum für Informatik
- ISBN: 978-3-95977-340-9
- DBLP: db/conf/wabi/wabi2024
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Document
Complete Volume
LIPIcs, Volume 312, WABI 2024, Complete Volume
Abstract
LIPIcs, Volume 312, WABI 2024, Complete Volume
Cite as
24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 1-454, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@Proceedings{pissis_et_al:LIPIcs.WABI.2024,
title = {{LIPIcs, Volume 312, WABI 2024, Complete Volume}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {1--454},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024},
URN = {urn:nbn:de:0030-drops-206430},
doi = {10.4230/LIPIcs.WABI.2024},
annote = {Keywords: LIPIcs, Volume 312, WABI 2024, Complete Volume}
}
Document
Front Matter
Front Matter, Table of Contents, Preface, Conference Organization
Abstract
Front Matter, Table of Contents, Preface, Conference Organization
Cite as
24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 0:i-0:xii, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{pissis_et_al:LIPIcs.WABI.2024.0,
author = {Pissis, Solon P. and Sung, Wing-Kin},
title = {{Front Matter, Table of Contents, Preface, Conference Organization}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {0:i--0:xii},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.0},
URN = {urn:nbn:de:0030-drops-206447},
doi = {10.4230/LIPIcs.WABI.2024.0},
annote = {Keywords: Front Matter, Table of Contents, Preface, Conference Organization}
}
Document
Invited Talk
Bioinformatics of Pathogens (Invited Talk)
Abstract
Genomic sequencing has become an important tool in identification and surveillance of human pathogens. Compared to large organisms, where our goal is to obtain high-quality sequences for detailed analysis, in pathogen sequencing the emphasis is often on optimization of cost and time. Consequently, sequencing of pathogens creates interesting computational challenges and development of new methods has a potential to significantly enhance applicability of the results in epidemiology and clinical practice. In my talk, I will give two examples: plasmid identification in bacterial isolates and genomic surveillance of wastewater for SARS-CoV-2. In both cases, application of better algorithms and modeling helps to improve the quality of analysis of very noisy data.
Cite as
Tomáš Vinař. Bioinformatics of Pathogens (Invited Talk). In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 1:1-1:2, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{vinar:LIPIcs.WABI.2024.1,
author = {Vina\v{r}, Tom\'{a}\v{s}},
title = {{Bioinformatics of Pathogens}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {1:1--1:2},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.1},
URN = {urn:nbn:de:0030-drops-206455},
doi = {10.4230/LIPIcs.WABI.2024.1},
annote = {Keywords: sequence analysis, genome assembly, neural networks, probabilistic modeling}
}
Document
On the Complexity of the Median and Closest Permutation Problems
Abstract
Genome rearrangements are events where large blocks of DNA exchange places during evolution. The analysis of these events is a promising tool for understanding evolutionary genomics, providing data for phylogenetic reconstruction based on genome rearrangement measures. Many pairwise rearrangement distances have been proposed, based on finding the minimum number of rearrangement events to transform one genome into the other, using some predefined operation. When more than two genomes are considered, we have the more challenging problem of rearrangement-based phylogeny reconstruction. Given a set of genomes and a distance notion, there are at least two natural ways to define the "target" genome. On the one hand, finding a genome that minimizes the sum of the distances from this to any other, called the median genome. On the other hand, finding a genome that minimizes the maximum distance to any other, called the closest genome. Considering genomes as permutations of distinct integers, some distance metrics have been extensively studied. We investigate the median and closest problems on permutations over the following metrics: breakpoint distance, swap distance, block-interchange distance, short-block-move distance, and transposition distance. In biological applications some values are usually very small, such as the solution value d or the number k of input permutations. For each of these metrics and parameters d or k, we analyze the closest and the median problems from the viewpoint of parameterized complexity. We obtain the following results: NP-hardness for finding the median/closest permutation regarding some metrics of distance, even for only k = 3 permutations; Polynomial kernels for the problems of finding the median permutation of all studied metrics, considering the target distance d as parameter; NP-hardness result for finding the closest permutation by short-block-moves; FPT algorithms and infeasibility of polynomial kernels for finding the closest permutation for some metrics when parameterized by the target distance d.
Cite as
Luís Cunha, Ignasi Sau, and Uéverton Souza. On the Complexity of the Median and Closest Permutation Problems. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 2:1-2:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{cunha_et_al:LIPIcs.WABI.2024.2,
author = {Cunha, Lu{\'\i}s and Sau, Ignasi and Souza, U\'{e}verton},
title = {{On the Complexity of the Median and Closest Permutation Problems}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {2:1--2:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.2},
URN = {urn:nbn:de:0030-drops-206468},
doi = {10.4230/LIPIcs.WABI.2024.2},
annote = {Keywords: Median problem, Closest problem, Genome rearrangements, Parameterized complexity}
}
Document
An Efficient Algorithm for the Reconciliation of a Gene Network and Species Tree
Abstract
The phylogenies of species and the genes they contain are similar but distinct, due to evolutionary events that affect genes but do not create new species. These events include gene duplication and loss, but also paralog exchange (non-allelic homologous recombination), where duplicate copies of a gene recombine. To account for paralog exchange, the evolutionary history of the genes must be represented in the form of a phylogenetic network. We reconstruct the interlinked evolution of the genes and species with reconciliations, which map the gene network into the species tree by explicitly accounting for these events. In previous work, we proposed the problem of reconciling a gene network and a species tree, but did not find an efficient solution for a general gene network. In this paper, we develop such a solution, and prove that it solves the most parsimonious reconciliation problem. Our algorithm is exponential only in the level of the gene network (with a base of 2), and we demonstrate that it is a practical solution through simulations. This allows, for the first time, a fine-grained study of the paralogy/orthology relationship between genes along their sequences.
Cite as
Yao-ban Chan. An Efficient Algorithm for the Reconciliation of a Gene Network and Species Tree. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 3:1-3:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{chan:LIPIcs.WABI.2024.3,
author = {Chan, Yao-ban},
title = {{An Efficient Algorithm for the Reconciliation of a Gene Network and Species Tree}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {3:1--3:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.3},
URN = {urn:nbn:de:0030-drops-206472},
doi = {10.4230/LIPIcs.WABI.2024.3},
annote = {Keywords: Reconciliation, recombination, paralog exchange, phylogenetic network, gene duplication, gene loss}
}
Document
MEM-Based Pangenome Indexing for k-mer Queries
Abstract
Pangenomes are growing in number and size, thanks to the prevalence of high-quality long-read assemblies. However, current methods for studying sequence composition and conservation within pangenomes have limitations. Methods based on graph pangenomes require a computationally expensive multiple-alignment step, which can leave out some variation. Indexes based on k-mers and de Bruijn graphs are limited to answering questions at a specific substring length k. We present Maximal Exact Match Ordered (MEMO), a pangenome indexing method based on maximal exact matches (MEMs) between sequences. A single MEMO index can handle arbitrary-length queries over pangenomic windows. MEMO enables both queries that test k-mer presence/absence (membership queries) and that count the number of genomes containing k-mers in a window (conservation queries). MEMO’s index for a pangenome of 89 human autosomal haplotypes fits in 2.04 GB, 8.8× smaller than a comparable KMC3 index and 11.4× smaller than a PanKmer index. MEMO indexes can be made smaller by sacrificing some counting resolution, with our decile-resolution HPRC index reaching 0.67 GB. MEMO can conduct a conservation query for 31-mers over the human leukocyte antigen locus in 13.89 seconds, 2.5× faster than other approaches. MEMO’s small index size, lack of k-mer length dependence, and efficient queries make it a flexible tool for studying and visualizing substring conservation in pangenomes.
Cite as
Stephen Hwang, Nathaniel K. Brown, Omar Y. Ahmed, Katharine M. Jenike, Sam Kovaka, Michael C. Schatz, and Ben Langmead. MEM-Based Pangenome Indexing for k-mer Queries. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 4:1-4:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{hwang_et_al:LIPIcs.WABI.2024.4,
author = {Hwang, Stephen and Brown, Nathaniel K. and Ahmed, Omar Y. and Jenike, Katharine M. and Kovaka, Sam and Schatz, Michael C. and Langmead, Ben},
title = {{MEM-Based Pangenome Indexing for k-mer Queries}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {4:1--4:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.4},
URN = {urn:nbn:de:0030-drops-206482},
doi = {10.4230/LIPIcs.WABI.2024.4},
annote = {Keywords: Pangenomics, Comparative genomics, Compressed indexing}
}
Document
Memoization on Shared Subtrees Accelerates Computations on Genealogical Forests
Abstract
The field of population genetics attempts to advance our understanding of evolutionary processes. It has applications, for example, in medical research, wildlife conservation, and - in conjunction with recent advances in ancient DNA sequencing technology - studying human migration patterns over the past few thousand years. The basic toolbox of population genetics includes genealogical trees, which describe the shared evolutionary history among individuals of the same species. They are calculated on the basis of genetic variations. However, in recombining organisms, a single tree is insufficient to describe the evolutionary history of the whole genome. Instead, a collection of correlated trees can be used, where each describes the evolutionary history of a consecutive region of the genome. The current corresponding state of-the-art data structure, tree sequences, compresses these genealogical trees via edit operations when moving from one tree to the next along the genome instead of storing the full, often redundant, description for each tree. We propose a new data structure, genealogical forests, which compresses the set of genealogical trees into a DAG. In this DAG identical subtrees that are shared across the input trees are encoded only once, thereby allowing for straight-forward memoization of intermediate results. Additionally, we provide a C++ implementation of our proposed data structure, called gfkit, which is 2.1 to 11.2 (median 4.0) times faster than the state-of-the-art tool on empirical and simulated datasets at computing important population genetics statistics such as the Allele Frequency Spectrum, Patterson’s f, the Fixation Index, Tajima’s D, pairwise Lowest Common Ancestors, and others. On Lowest Common Ancestor queries with more than two samples as input, gfkit scales asymptotically better than the state-of-the-art, and is thus up to 990 times faster. In conclusion, our proposed data structure compresses genealogical trees by storing shared subtrees only once, thereby enabling straight-forward memoization of intermediate results, yielding a substantial runtime reduction and a potentially more intuitive data representation over the state-of-the-art. Our improvements will boost the development of novel analyses and models in the field of population genetics and increases scalability to ever-growing genomic datasets.
Cite as
Lukas Hübner and Alexandros Stamatakis. Memoization on Shared Subtrees Accelerates Computations on Genealogical Forests. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 5:1-5:22, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{hubner_et_al:LIPIcs.WABI.2024.5,
author = {H\"{u}bner, Lukas and Stamatakis, Alexandros},
title = {{Memoization on Shared Subtrees Accelerates Computations on Genealogical Forests}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {5:1--5:22},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.5},
URN = {urn:nbn:de:0030-drops-206499},
doi = {10.4230/LIPIcs.WABI.2024.5},
annote = {Keywords: bioinformatics, population genetics, algorithms}
}
Document
Cosine Similarity Estimation Using FracMinHash: Theoretical Analysis, Safety Conditions, and Implementation
Abstract
Motivation. The increasing number and volume of genomic and metagenomic data necessitates scalable and robust computational models for precise analysis. Sketching techniques utilizing k-mers from a biological sample have proven to be useful for large-scale analyses. In recent years, FracMinHash has emerged as a popular sketching technique and has been used in several useful applications. Recent studies on FracMinHash proved unbiased estimators for the containment and Jaccard indices. However, theoretical investigations for other metrics, such as the cosine similarity, are still lacking.
Theoretical contributions. In this paper, we present a theoretical framework for estimating cosine similarity from FracMinHash sketches. We establish conditions under which this estimation is sound, and recommend a minimum scale factor s for accurate results. Experimental evidence supports our theoretical findings.
Practical contributions. We also present frac-kmc, a fast and efficient FracMinHash sketch generator program. frac-kmc is the fastest known FracMinHash sketch generator, delivering accurate and precise results for cosine similarity estimation on real data. We show that by computing FracMinHash sketches using frac-kmc, we can estimate pairwise cosine similarity speedily and accurately on real data. frac-kmc is freely available here: https://github.com/KoslickiLab/frac-kmc/.
Cite as
Mahmudur Rahman Hera and David Koslicki. Cosine Similarity Estimation Using FracMinHash: Theoretical Analysis, Safety Conditions, and Implementation. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 6:1-6:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{hera_et_al:LIPIcs.WABI.2024.6,
author = {Hera, Mahmudur Rahman and Koslicki, David},
title = {{Cosine Similarity Estimation Using FracMinHash: Theoretical Analysis, Safety Conditions, and Implementation}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {6:1--6:16},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.6},
URN = {urn:nbn:de:0030-drops-206502},
doi = {10.4230/LIPIcs.WABI.2024.6},
annote = {Keywords: Hashing, sketching, FracMinHash, Min-Hash, k-mer, similarity, theory}
}
Document
Sapling: Inferring and Summarizing Tumor Phylogenies from Bulk Data Using Backbone Trees
Abstract
Cancer phylogenies are key to understanding tumor evolution. There exist many important downstream analyses that take as input a single or a small number of trees. However, due to uncertainty, one typically infers many, equally-plausible phylogenies from bulk DNA sequencing data of tumors. We introduce Sapling, a heuristic method to solve the Backbone Tree Inference from Reads problem, which seeks a small set of backbone trees on a smaller subset of mutations that collectively summarize the entire solution space. Sapling also includes a greedy algorithm to solve the Backbone Tree Expansion from Reads problem, which aims to expand an inferred backbone tree into a full tree. We prove that both problems are NP-hard. On simulated and real data, we demonstrate that Sapling is capable of inferring high-quality backbone trees that adequately summarize the solution space and that can be expanded into full trees.
Cite as
Yuanyuan Qi and Mohammed El-Kebir. Sapling: Inferring and Summarizing Tumor Phylogenies from Bulk Data Using Backbone Trees. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 7:1-7:19, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{qi_et_al:LIPIcs.WABI.2024.7,
author = {Qi, Yuanyuan and El-Kebir, Mohammed},
title = {{Sapling: Inferring and Summarizing Tumor Phylogenies from Bulk Data Using Backbone Trees}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {7:1--7:19},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.7},
URN = {urn:nbn:de:0030-drops-206518},
doi = {10.4230/LIPIcs.WABI.2024.7},
annote = {Keywords: Cancer, intra-tumor heterogeneity, consensus, maximum agreement}
}
Document
Applying the Safe-And-Complete Framework to Practical Genome Assembly
Abstract
Despite the long history of genome assembly research, there remains a large gap between the theoretical and practical work. There is practical software with little theoretical underpinning of accuracy on one hand and theoretical algorithms which have not been adopted in practice on the other. In this paper we attempt to bridge the gap between theory and practice by showing how the theoretical safe-and-complete framework can be integrated into existing assemblers in order to improve contiguity. The optimal algorithm in this framework, called the omnitig algorithm, has not been used in practice due to its complexity and its lack of robustness to real data. Instead, we pursue a simplified notion of omnitigs (simple omnitigs), giving an efficient algorithm to compute them and demonstrating their safety under certain conditions. We modify two assemblers (wtdbg2 and Flye) by replacing their unitig algorithm with the simple omnitig algorithm. We test our modifications using real HiFi data from the D. melanogaster and the C. elegans genomes. Our modified algorithms lead to a substantial improvement in alignment-based contiguity, with negligible additional computational costs and either no or a small increase in the number of misassemblies.
Cite as
Sebastian Schmidt, Santeri Toivonen, Paul Medvedev, and Alexandru I. Tomescu. Applying the Safe-And-Complete Framework to Practical Genome Assembly. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 8:1-8:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{schmidt_et_al:LIPIcs.WABI.2024.8,
author = {Schmidt, Sebastian and Toivonen, Santeri and Medvedev, Paul and Tomescu, Alexandru I.},
title = {{Applying the Safe-And-Complete Framework to Practical Genome Assembly}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {8:1--8:16},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.8},
URN = {urn:nbn:de:0030-drops-206520},
doi = {10.4230/LIPIcs.WABI.2024.8},
annote = {Keywords: Genome assembly, Omnitigs, Safe-and-complete framework, graph algorithm, HiFi sequencing data, Assembly evaluation}
}
Document
Orientability of Undirected Phylogenetic Networks to a Desired Class: Practical Algorithms and Application to Tree-Child Orientation
Abstract
The 𝒞-Orientation problem asks whether it is possible to orient an undirected graph to a directed phylogenetic network of a desired class 𝒞, and to find such an orientation if one exists. The problem can arise when visualising evolutionary data, for example, because popular phylogenetic network reconstruction methods such as Neighbor-Net are distance-based and thus inevitably produce undirected graphs. The complexity of 𝒞-Orientation remains open for many classes 𝒞, including binary tree-child networks, and practical methods are still lacking. In this paper, we propose an exponential but practically efficient FPT algorithm for 𝒞-Orientation, which is parameterised by the reticulation number and the maximum size of minimal basic cycles used in the computation. We also present a very fast heuristic for Tree-Child Orientation. To evaluate the empirical performance of the proposed methods, we compared their accuracy and execution time for Tree-Child Orientation with those of an exponential time 𝒞-orientation algorithm from the literature. Our experiments show that the proposed exact algorithm is significantly faster than the state-of-the-art exponential time algorithm. The proposed heuristic runs even faster but the accuracy decreases as the reticulation number increases.
Cite as
Tsuyoshi Urata, Manato Yokoyama, and Momoko Hayamizu. Orientability of Undirected Phylogenetic Networks to a Desired Class: Practical Algorithms and Application to Tree-Child Orientation. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 9:1-9:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{urata_et_al:LIPIcs.WABI.2024.9,
author = {Urata, Tsuyoshi and Yokoyama, Manato and Hayamizu, Momoko},
title = {{Orientability of Undirected Phylogenetic Networks to a Desired Class: Practical Algorithms and Application to Tree-Child Orientation}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {9:1--9:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.9},
URN = {urn:nbn:de:0030-drops-206531},
doi = {10.4230/LIPIcs.WABI.2024.9},
annote = {Keywords: Phylogenetic Networks, Tree-Child Networks, Graph Orientation Algorithms}
}
Document
b-move: Faster Bidirectional Character Extensions in a Run-Length Compressed Index
Abstract
Due to the increasing availability of high-quality genome sequences, pan-genomes are gradually replacing single consensus reference genomes in many bioinformatics pipelines to better capture genetic diversity. Traditional bioinformatics tools using the FM-index face memory limitations with such large genome collections. Recent advancements in run-length compressed indices like Gagie et al.’s r-index and Nishimoto and Tabei’s move structure, alleviate memory constraints but focus primarily on backward search for MEM-finding. Arakawa et al.’s br-index initiates complete approximate pattern matching using bidirectional search in run-length compressed space, but with significant computational overhead due to complex memory access patterns. We introduce b-move, a novel bidirectional extension of the move structure, enabling fast, cache-efficient bidirectional character extensions in run-length compressed space. It achieves bidirectional character extensions up to 8 times faster than the br-index, closing the performance gap with FM-index-based alternatives, while maintaining the br-index’s favorable memory characteristics. For example, all available complete E. coli genomes on NCBI’s RefSeq collection can be compiled into a b-move index that fits into the RAM of a typical laptop. Thus, b-move proves practical and scalable for pan-genome indexing and querying. We provide a C++ implementation of b-move, supporting efficient lossless approximate pattern matching including locate functionality, available at https://github.com/biointec/b-move under the AGPL-3.0 license.
Cite as
Lore Depuydt, Luca Renders, Simon Van de Vyver, Lennart Veys, Travis Gagie, and Jan Fostier. b-move: Faster Bidirectional Character Extensions in a Run-Length Compressed Index. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 10:1-10:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{depuydt_et_al:LIPIcs.WABI.2024.10,
author = {Depuydt, Lore and Renders, Luca and Van de Vyver, Simon and Veys, Lennart and Gagie, Travis and Fostier, Jan},
title = {{b-move: Faster Bidirectional Character Extensions in a Run-Length Compressed Index}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {10:1--10:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.10},
URN = {urn:nbn:de:0030-drops-206546},
doi = {10.4230/LIPIcs.WABI.2024.10},
annote = {Keywords: Pan-genomics, FM-index, r-index, Move Structure, Bidirectional Search, Approximate Pattern Matching, Lossless Alignment, Cache Efficiency}
}
Document
The mod-minimizer: A Simple and Efficient Sampling Algorithm for Long k-mers
Abstract
Motivation. Given a string S, a minimizer scheme is an algorithm defined by a triple (k,w,𝒪) that samples a subset of k-mers (k-long substrings) from a string S. Specifically, it samples the smallest k-mer according to the order 𝒪 from each window of w consecutive k-mers in S. Because consecutive windows can sample the same k-mer, the set of the sampled k-mers is typically much smaller than S. More generally, we consider substring sampling algorithms that respect a window guarantee: at least one k-mer must be sampled from every window of w consecutive k-mers. As a sampled k-mer is uniquely identified by its absolute position in S, we can define the density of a sampling algorithm as the fraction of distinct sampled positions. Good methods have low density which, by respecting the window guarantee, is lower bounded by 1/w. It is however difficult to design a sequence-agnostic algorithm with provably optimal density. In practice, the order 𝒪 is usually implemented using a pseudo-random hash function to obtain the so-called random minimizer. This scheme is simple to implement, very fast to compute even in streaming fashion, and easy to analyze. However, its density is almost a factor of 2 away from the lower bound for large windows.
Methods. In this work we introduce mod-sampling, a two-step sampling algorithm to obtain new minimizer schemes. Given a (small) parameter t, the mod-sampling algorithm finds the position p of the smallest t-mer in a window. It then samples the k-mer at position pod w. The lr-minimizer uses t = k-w and the mod-minimizer uses t≡ k (mod w).
Results. These new schemes have provably lower density than random minimizers and other schemes when k is large compared to w, while being as fast to compute. Importantly, the mod-minimizer achieves optimal density when k → ∞. Although the mod-minimizer is not the first method to achieve optimal density for large k, its proof of optimality is simpler than previous work.
We provide pseudocode for a number of other methods and compare to them. In practice, the mod-minimizer has considerably lower density than the random minimizer and other state-of-the-art methods, like closed syncmers and miniception, when k > w. We plugged the mod-minimizer into SSHash, a k-mer dictionary based on minimizers. For default parameters (w,k) = (11,21), space usage decreases by 15% when indexing the whole human genome (GRCh38), while maintaining its fast query time.
Cite as
Ragnar Groot Koerkamp and Giulio Ermanno Pibiri. The mod-minimizer: A Simple and Efficient Sampling Algorithm for Long k-mers. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 11:1-11:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{grootkoerkamp_et_al:LIPIcs.WABI.2024.11,
author = {Groot Koerkamp, Ragnar and Pibiri, Giulio Ermanno},
title = {{The mod-minimizer: A Simple and Efficient Sampling Algorithm for Long k-mers}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {11:1--11:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.11},
URN = {urn:nbn:de:0030-drops-206552},
doi = {10.4230/LIPIcs.WABI.2024.11},
annote = {Keywords: Minimizers, Randomized algorithms, Sketching, Hashing}
}
Document
Reconstructing Rearrangement Phylogenies of Natural Genomes
Abstract
We study the classical problem of inferring ancestral genomes from a set of extant genomes under a given phylogeny, known as the Small Parsimony Problem (SPP). Genomes are represented as sequences of oriented markers, organized in one or more linear or circular chromosomes. Any marker may appear in several copies, without restriction on orientation or genomic location, known as the natural genomes model. Evolutionary events along the branches of the phylogeny encompass large scale rearrangements, including segmental inversions, translocations, gain and loss (DCJ-indel model).
Even under simpler rearrangement models, such as the classical breakpoint model without duplicates, the SPP is computationally intractable. Nevertheless, the SPP for natural genomes under the DCJ-indel model has been studied recently, with limited success. Here, we improve on that earlier work, giving a highly optimized ILP that is able to solve the SPP for sufficiently small phylogenies and gene families. A notable improvement w.r.t. the previous result is an optimized way of handling both circular and linear chromosomes. This is especially relevant to the SPP, since the chromosomal structure of ancestral genomes is unknown and the solution space for this chromosomal structure is typically large.
We benchmark our method on simulated and real data. On simulated phylogenies we observe a considerable performance improvement on problems that include linear chromosomes. And even when the ground truth contains only one circular chromosome per genome, our method outperforms its predecessor due to its optimized handling of the solution space. The practical advantage becomes also visible in an analysis of seven Anopheles taxa.
Cite as
Leonard Bohnenkämper, Jens Stoye, and Daniel Dörr. Reconstructing Rearrangement Phylogenies of Natural Genomes. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 12:1-12:16, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{bohnenkamper_et_al:LIPIcs.WABI.2024.12,
author = {Bohnenk\"{a}mper, Leonard and Stoye, Jens and D\"{o}rr, Daniel},
title = {{Reconstructing Rearrangement Phylogenies of Natural Genomes}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {12:1--12:16},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.12},
URN = {urn:nbn:de:0030-drops-206564},
doi = {10.4230/LIPIcs.WABI.2024.12},
annote = {Keywords: genome rearrangement, ancestral reconstruction, small parsimony, integer linear programming, double-cut-and-join}
}
Document
PLA-index: A k-mer Index Exploiting Rank Curve Linearity
Abstract
Given a sorted list of k-mers S, the rank curve of S is the function mapping a k-mer from the k-mer universe to the location in S where it either first appears or would be inserted. An exciting recent development is the observation that, for certain datasets, the rank curve is predictable and can be exploited to create small search indices. In this paper, we develop a novel search index that first estimates a k-mer’s rank using a piece-wise linear approximation of the rank curve and then does a local search to determine the precise location of the k-mer in the list. We combine ideas from previous approaches and supplement them with an innovative data representation strategy that substantially reduces space usage. Our PLA-index uses an order of magnitude less space than Sapling and uses less than half the space of the PGM-index, for roughly the same query time. For example, using only 9 MiB of memory, it can narrow down the position of k-mer in the suffix array of the human genome to within 255 positions. Furthermore, we demonstrate the potential of our approach to impact a variety of downstream applications. First, the PLA-index halves the time of binary search on the suffix array of the human genome. Second, the PLA-index reduces the space of a direct-access lookup table by 76 percent, without increasing the run time. Third, we plug the PLA-index into a state-of-the-art read aligner Strobealign and replace a 2 GiB component with a PLA-index of size 1.5 MiB, without significantly effecting runtime. The software and reproducibility information is freely available at https://github.com/medvedevgroup/pla-index.
Cite as
Md. Hasin Abrar and Paul Medvedev. PLA-index: A k-mer Index Exploiting Rank Curve Linearity. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 13:1-13:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{abrar_et_al:LIPIcs.WABI.2024.13,
author = {Abrar, Md. Hasin and Medvedev, Paul},
title = {{PLA-index: A k-mer Index Exploiting Rank Curve Linearity}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {13:1--13:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.13},
URN = {urn:nbn:de:0030-drops-206578},
doi = {10.4230/LIPIcs.WABI.2024.13},
annote = {Keywords: K-mer index, Piece-wise linear approximation, Learned index}
}
Document
A Unifying Taxonomy of Pattern Matching in Degenerate Strings and Founder Graphs
Abstract
Elastic Degenerate (ED) strings and Elastic Founder (EF) graphs are two versions of acyclic components of pangenomes. Both ED strings and EF graphs (which we collectively name variable strings) extend the well-known notion of indeterminate string. Recent work has extensively investigated algorithmic tasks over these structures, and over several other variable strings notions that they generalise. Among such tasks, the basic operation of matching a pattern into a text, which can serve as a toolkit for many pangenomic data analyses using these data structures, deserves special attention. In this paper we: (1) highlight a clear taxonomy within both ED strings and EF graphs ranging through variable strings of all types, from the linear string up to the most general one; (2) investigate the problem PvarT(X,Y) of matching a solid or variable pattern of type X into a variable text of type Y; (3) using as a reference the quadratic conditional lower bounds that are known for PvarT(solid,ED) and PvarT(solid,EF), for all possible types of variable strings X and Y we either prove the quadratic conditional lower bound for PvarT(X,Y), or provide non-trivial, often sub-quadratic, upper bounds, also exploiting the above-mentioned taxonomy.
Cite as
Rocco Ascone, Giulia Bernardini, Alessio Conte, Massimo Equi, Esteban Gabory, Roberto Grossi, and Nadia Pisanti. A Unifying Taxonomy of Pattern Matching in Degenerate Strings and Founder Graphs. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 14:1-14:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{ascone_et_al:LIPIcs.WABI.2024.14,
author = {Ascone, Rocco and Bernardini, Giulia and Conte, Alessio and Equi, Massimo and Gabory, Esteban and Grossi, Roberto and Pisanti, Nadia},
title = {{A Unifying Taxonomy of Pattern Matching in Degenerate Strings and Founder Graphs}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {14:1--14:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.14},
URN = {urn:nbn:de:0030-drops-206586},
doi = {10.4230/LIPIcs.WABI.2024.14},
annote = {Keywords: Pangenomics, pattern matching, degenerate string, founder graph, fine-grained complexity}
}
Document
Swiftly Identifying Strongly Unique k-Mers
Abstract
Motivation. Short DNA sequences of length k that appear in a single location (e.g., at a single genomic position, in a single species from a larger set of species, etc.) are called unique k-mers. They are useful for placing sequenced DNA fragments at the correct location without computing alignments and without ambiguity. However, they are not necessarily robust: A single basepair change may turn a unique k-mer into a different one that may in fact be present at one or more different locations, which may give confusing or contradictory information when attempting to place a read by its k-mer content. A more robust concept are strongly unique k-mers, i.e., unique k-mers for which no Hamming-distance-1 neighbor with conflicting information exists in all of the considered sequences. Given a set of k-mers, it is therefore of interest to have an efficient method that can distinguish k-mers with a Hamming-distance-1 neighbor in the collection from those that do not.
Results. We present engineered algorithms to identify and mark within a set K of (canonical) k-mers all elements that have a Hamming-distance-1 neighbor in the same set. One algorithm is based on recursively running a 4-way comparison on sub-intervals of the sorted set. The other algorithm is based on bucketing and running a pairwise bit-parallel Hamming distance test on small buckets of the sorted set. Both methods consider canonical k-mers (i.e., taking reverse complements into account) and allow for efficient parallelization. The methods have been implemented and applied in practice to sets consisting of several billions of k-mers. An optimized combined approach running with 16 threads on a 16-core workstation, yields wall-clock running times below 20 seconds on the 2.5 billion distinct 31-mers of the human telomere-to-telomere reference genome.
Availability. An implementation can be found at https://gitlab.com/rahmannlab/strong-k-mers.
Cite as
Jens Zentgraf and Sven Rahmann. Swiftly Identifying Strongly Unique k-Mers. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 15:1-15:15, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{zentgraf_et_al:LIPIcs.WABI.2024.15,
author = {Zentgraf, Jens and Rahmann, Sven},
title = {{Swiftly Identifying Strongly Unique k-Mers}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {15:1--15:15},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.15},
URN = {urn:nbn:de:0030-drops-206593},
doi = {10.4230/LIPIcs.WABI.2024.15},
annote = {Keywords: k-mer, Hamming distance, strong uniqueness, parallelization, algorithm engineering}
}
Document
Finding Maximum Common Contractions Between Phylogenetic Networks
Abstract
In this paper, we lay the groundwork on the comparison of phylogenetic networks based on edge contractions and expansions as edit operations, as originally proposed by Robinson and Foulds to compare trees. We prove that these operations connect the space of all phylogenetic networks on the same set of leaves, even if we forbid contractions that create cycles. This allows to define an operational distance on this space, as the minimum number of contractions and expansions required to transform one network into another. We highlight the difference between this distance and the computation of the maximum common contraction between two networks. Given its ability to outline a common structure between them, which can provide valuable biological insights, we study the algorithmic aspects of the latter. We first prove that computing a maximum common contraction between two networks is NP-hard, even when the maximum degree, the size of the common contraction, or the number of leaves is bounded. We also provide lower bounds to the problem based on the Exponential-Time Hypothesis. Nonetheless, we do provide a polynomial-time algorithm for weakly galled trees, a generalization of galled trees.
Cite as
Bertrand Marchand, Nadia Tahiri, Olivier Tremblay-Savard, and Manuel Lafond. Finding Maximum Common Contractions Between Phylogenetic Networks. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 16:1-16:24, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{marchand_et_al:LIPIcs.WABI.2024.16,
author = {Marchand, Bertrand and Tahiri, Nadia and Tremblay-Savard, Olivier and Lafond, Manuel},
title = {{Finding Maximum Common Contractions Between Phylogenetic Networks}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {16:1--16:24},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.16},
URN = {urn:nbn:de:0030-drops-206606},
doi = {10.4230/LIPIcs.WABI.2024.16},
annote = {Keywords: Phylogenetic networks, contractions, algorithms, weakly galled trees}
}
Document
A*PA2: Up to 19× Faster Exact Global Alignment
Abstract
Motivation. Pairwise alignment is at the core of computational biology. Most commonly used exact methods are either based on O(ns) band doubling or O(n+s²) diagonal transition, where n is the sequence length and s the number of errors. However, as the length of sequences has grown, these exact methods are often replaced by approximate methods based on e.g. seed-and-extend and heuristics to bound the computed region. We would like to develop an exact method that matches the performance of these approximate methods.
Recently, Astarix introduced the A* shortest path algorithm with the seed heuristic for exact sequence-to-graph alignment. A*PA adapted and improved this for pairwise sequence alignment and achieves near-linear runtime when divergence (error rate) is low, at the cost of being very slow when divergence is high.
Methods. We introduce A*PA2, an exact global pairwise aligner with respect to edit distance. The goal of A*PA2 is to unify the near-linear runtime of A*PA on similar sequences with the efficiency of dynamic programming (DP) based methods. Like Edlib, A*PA2 uses Ukkonen’s band doubling in combination with Myers' bitpacking. A*PA2 1) uses large block sizes inspired by Block Aligner, 2) extends this with SIMD (single instruction, multiple data), 3) introduces a new profile for efficient computations, 4) introduces a new optimistic technique for traceback based on diagonal transition, 5) avoids recomputation of states where possible, and 6) applies the heuristics developed in A*PA and improves them using pre-pruning.
Results. With the first 4 engineering optimizations, A*PA2-simple has complexity O(ns) and is 6× to 8× faster than Edlib for sequences ≥ 10 kbp. A*PA2-full also includes the heuristic and is often near-linear in practice for sequences with small divergence. The average runtime of A*PA2 is 19× faster than the exact aligners BiWFA and Edlib on >500 kbp long ONT (Oxford Nanopore Technologies) reads of a human genome having 6% divergence on average. On shorter ONT reads of 11% average divergence the speedup is 5.6× (avg. length 11 kbp) and 0.81× (avg. length 800 bp). On all tested datasets, A*PA2 is competitive with or faster than approximate methods.
Cite as
Ragnar Groot Koerkamp. A*PA2: Up to 19× Faster Exact Global Alignment. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 17:1-17:25, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{grootkoerkamp:LIPIcs.WABI.2024.17,
author = {Groot Koerkamp, Ragnar},
title = {{A*PA2: Up to 19× Faster Exact Global Alignment}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {17:1--17:25},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.17},
URN = {urn:nbn:de:0030-drops-206610},
doi = {10.4230/LIPIcs.WABI.2024.17},
annote = {Keywords: Edit distance, Pairwise alignment, A*, Shortest path, Dynamic programming}
}
Document
RNA Triplet Repeats: Improved Algorithms for Structure Prediction and Interactions
Abstract
RNAs composed of Triplet Repeats (TR) have recently attracted much attention in the field of synthetic biology. We study the mimimum free energy (MFE) secondary structures of such RNAs and give improved algorithms to compute the MFE and the partition function. Furthermore, we study the interaction of multiple RNAs and design a new algorithm for computing MFE and partition function for RNA-RNA interactions, improving the previously known factorial running time to exponential. In the case of TR, we show computational hardness but still obtain a parameterized algorithm. Finally, we propose a polynomial-time algorithm for computing interactions from a base set of RNA strands and conduct experiments on the interaction of TR based on this algorithm. For instance, we study the probability that a base pair is formed between two strands with the same triplet pattern, allowing an assessment of a notion of orthogonality between TR.
Cite as
Kimon Boehmer, Sarah J. Berkemer, Sebastian Will, and Yann Ponty. RNA Triplet Repeats: Improved Algorithms for Structure Prediction and Interactions. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 18:1-18:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{boehmer_et_al:LIPIcs.WABI.2024.18,
author = {Boehmer, Kimon and Berkemer, Sarah J. and Will, Sebastian and Ponty, Yann},
title = {{RNA Triplet Repeats: Improved Algorithms for Structure Prediction and Interactions}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {18:1--18:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.18},
URN = {urn:nbn:de:0030-drops-206625},
doi = {10.4230/LIPIcs.WABI.2024.18},
annote = {Keywords: RNA folding, RNA interactions, triplet repeats, dynamic programming, NP-hardness}
}
Document
RNA Inverse Folding Can Be Solved in Linear Time for Structures Without Isolated Stacks or Base Pairs
Abstract
Inverse folding is a classic instance of negative RNA design which consists in finding a sequence that uniquely folds into a target secondary structure with respect to energy minimization. A breakthrough result of Bonnet et al. shows that, even in simple base pairs-based (BP) models, the decision version of a mildly constrained version of inverse folding is NP-hard.
In this work, we show that inverse folding can be solved in linear time for a large collection of targets, including every structure that contains no isolated BP and no isolated stack (or, equivalently, when all helices consist of 3^{+} base pairs). For structures featuring shorter helices, our linear algorithm is no longer guaranteed to produce a solution, but still does so for a large proportion of instances.
Our approach introduces a notion of modulo m-separability, generalizing a property pioneered by Hales et al. Separability is a sufficient condition for the existence of a solution to the inverse folding problem. We show that, for any input secondary structure of length n, a modulo m-separated sequence can be produced in time 𝒪(n 2^m) anytime such a sequence exists. Meanwhile, we show that any structure consisting of 3^{+} base pairs is either trivially non-designable, or always admits a modulo-2 separated solution (m = 2). Solution sequences can thus be produced in linear time, and even be uniformly generated within the set of modulo-2 separable sequences.
Cite as
Théo Boury, Laurent Bulteau, and Yann Ponty. RNA Inverse Folding Can Be Solved in Linear Time for Structures Without Isolated Stacks or Base Pairs. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 19:1-19:23, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{boury_et_al:LIPIcs.WABI.2024.19,
author = {Boury, Th\'{e}o and Bulteau, Laurent and Ponty, Yann},
title = {{RNA Inverse Folding Can Be Solved in Linear Time for Structures Without Isolated Stacks or Base Pairs}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {19:1--19:23},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.19},
URN = {urn:nbn:de:0030-drops-206632},
doi = {10.4230/LIPIcs.WABI.2024.19},
annote = {Keywords: RNA structure, String Design, Parameterized Complexity, Uniform Sampling}
}
Document
The Path-Label Reconciliation (PLR) Dissimilarity Measure for Gene Trees
Abstract
In this study, we investigate the problem of comparing gene trees reconciled with the same species tree using a novel semi-metric, called the Path-Label Reconciliation (PLR) dissimilarity measure. This approach not only quantifies differences in the topology of reconciled gene trees, but also considers discrepancies in predicted ancestral gene-species maps and speciation/duplication events, offering a refinement of existing metrics such as Robinson-Foulds (RF) and their labeled extensions LRF and ELRF. A tunable parameter α also allows users to adjust the balance between its species map and event labeling components. We show that PLR can be computed in linear time and that it is a semi-metric. We also discuss the diameters of reconciled gene tree measures, which are important in practice for normalization, and provide initial bounds on PLR, LRF, and ELRF.
To validate PLR, we simulate reconciliations and perform comparisons with LRF and ELRF. The results show that PLR provides a more evenly distributed range of distances, making it less susceptible to overestimating differences in the presence of small topological changes, while at the same time being computationally efficient. Our findings suggest that the theoretical diameter is rarely reached in practice. The PLR measure advances phylogenetic reconciliation by combining theoretical rigor with practical applicability. Future research will refine its mathematical properties, explore its performance on different tree types, and integrate it with existing bioinformatics tools for large-scale evolutionary analyses. The open source code is available at: https://pypi.org/project/parle/.
Cite as
Alitzel López Sánchez, José Antonio Ramírez-Rafael, Alejandro Flores-Lamas, Maribel Hernández-Rosales, and Manuel Lafond. The Path-Label Reconciliation (PLR) Dissimilarity Measure for Gene Trees. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 20:1-20:21, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{lopezsanchez_et_al:LIPIcs.WABI.2024.20,
author = {L\'{o}pez S\'{a}nchez, Alitzel and Ram{\'\i}rez-Rafael, Jos\'{e} Antonio and Flores-Lamas, Alejandro and Hern\'{a}ndez-Rosales, Maribel and Lafond, Manuel},
title = {{The Path-Label Reconciliation (PLR) Dissimilarity Measure for Gene Trees}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {20:1--20:21},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.20},
URN = {urn:nbn:de:0030-drops-206645},
doi = {10.4230/LIPIcs.WABI.2024.20},
annote = {Keywords: Reconciliation, gene trees, species trees, evolutionary scenarios}
}
Document
McDag: Indexing Maximal Common Subsequences in Practice
Abstract
Analyzing and comparing sequences of symbols is among the most fundamental problems in computer science, possibly even more so in bioinformatics. Maximal Common Subsequences (MCSs), i.e., inclusion-maximal sequences of non-contiguous symbols common to two or more strings, have only recently received attention in this area, despite being a basic notion and a natural generalization of more common tools like Longest Common Substrings/Subsequences. In this paper we simplify and engineer recent advancements on MCSs into a practical tool called McDag, the first publicly available tool that can index MCSs of real genomic data. We demonstrate that our tool can index sequences exceeding 10,000 base pairs within minutes, utilizing only 4-7% more than the minimum required nodes, while also extracting relevant insights.
Cite as
Giovanni Buzzega, Alessio Conte, Roberto Grossi, and Giulia Punzi. McDag: Indexing Maximal Common Subsequences in Practice. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 21:1-21:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{buzzega_et_al:LIPIcs.WABI.2024.21,
author = {Buzzega, Giovanni and Conte, Alessio and Grossi, Roberto and Punzi, Giulia},
title = {{McDag: Indexing Maximal Common Subsequences in Practice}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {21:1--21:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.21},
URN = {urn:nbn:de:0030-drops-206650},
doi = {10.4230/LIPIcs.WABI.2024.21},
annote = {Keywords: Index data structure, DAG, Common subsequence, Inclusion-wise maximality, LCS}
}
Document
Anchorage Accurately Assembles Anchor-Flanked Synthetic Long Reads
Abstract
Modern sequencing technologies allow for the addition of short-sequence tags, known as anchors, to both ends of a captured molecule. Anchors are useful in assembling the full-length sequence of a captured molecule as they can be used to accurately determine the endpoints. One representative of such anchor-enabled technology is LoopSeq Solo, a synthetic long read (SLR) sequencing protocol. LoopSeq Solo also achieves ultra-high sequencing depth and high purity of short reads covering the entire captured molecule. Despite the availability of many assembly methods, constructing full-length sequence from these anchor-enabled, ultra-high coverage sequencing data remains challenging due to the complexity of the underlying assembly graphs and the lack of specific algorithms leveraging anchors. We present Anchorage, a novel assembler that performs anchor-guided assembly for ultra-high-depth sequencing data. Anchorage starts with a kmer-based approach for precise estimation of molecule lengths. It then formulates the assembly problem as finding an optimal path that connects the two nodes determined by anchors in the underlying compact de Bruijn graph. The optimality is defined as maximizing the weight of the smallest node while matching the estimated sequence length. Anchorage uses a modified dynamic programming algorithm to efficiently find the optimal path. Through both simulations and real data, we show that Anchorage outperforms existing assembly methods, particularly in the presence of sequencing artifacts. Anchorage fills the gap in assembling anchor-enabled data. We anticipate its broad use as anchor-enabled sequencing technologies become prevalent. Anchorage is freely available at https://github.com/Shao-Group/anchorage; the scripts and documents that can reproduce all experiments in this manuscript are available at https://github.com/Shao-Group/anchorage-test.
Cite as
Xiaofei Carl Zang, Xiang Li, Kyle Metcalfe, Tuval Ben-Yehezkel, Ryan Kelley, and Mingfu Shao. Anchorage Accurately Assembles Anchor-Flanked Synthetic Long Reads. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 22:1-22:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{zang_et_al:LIPIcs.WABI.2024.22,
author = {Zang, Xiaofei Carl and Li, Xiang and Metcalfe, Kyle and Ben-Yehezkel, Tuval and Kelley, Ryan and Shao, Mingfu},
title = {{Anchorage Accurately Assembles Anchor-Flanked Synthetic Long Reads}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {22:1--22:17},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.22},
URN = {urn:nbn:de:0030-drops-206660},
doi = {10.4230/LIPIcs.WABI.2024.22},
annote = {Keywords: Genome assembly, de Bruijn graph, synthetic long reads, anchor-guided assembly, LoopSeq}
}
Document
AlfaPang: Alignment Free Algorithm for Pangenome Graph Construction
Abstract
The success of pangenome-based approaches to genomics analysis depends largely on the existence of efficient methods for constructing pangenome graphs that are applicable to large genome collections.
In the current paper we present AlfaPang, a new pangenome graph building algorithm. AlfaPang is based on a novel alignment-free approach that allows to construct pangenome graphs using significantly less computational resources than state-of-the-art tools. The code of AlfaPang is freely available at https://github.com/AdamCicherski/AlfaPang.
Cite as
Adam Cicherski, Anna Lisiecka, and Norbert Dojer. AlfaPang: Alignment Free Algorithm for Pangenome Graph Construction. In 24th International Workshop on Algorithms in Bioinformatics (WABI 2024). Leibniz International Proceedings in Informatics (LIPIcs), Volume 312, pp. 23:1-23:18, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2024)
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@InProceedings{cicherski_et_al:LIPIcs.WABI.2024.23,
author = {Cicherski, Adam and Lisiecka, Anna and Dojer, Norbert},
title = {{AlfaPang: Alignment Free Algorithm for Pangenome Graph Construction}},
booktitle = {24th International Workshop on Algorithms in Bioinformatics (WABI 2024)},
pages = {23:1--23:18},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
ISBN = {978-3-95977-340-9},
ISSN = {1868-8969},
year = {2024},
volume = {312},
editor = {Pissis, Solon P. and Sung, Wing-Kin},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
address = {Dagstuhl, Germany},
URL = {https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2024.23},
URN = {urn:nbn:de:0030-drops-206673},
doi = {10.4230/LIPIcs.WABI.2024.23},
annote = {Keywords: pangenome, variation graph, genome alignment, population genomics}
}