21.
Khorsand, Parsoa; Denti, Luca; Consortium, Human Genome Structural Variant; Bonizzoni, Paola; Chikhi, Rayan; Hormozdiari, Fereydoun
Comparative genome analysis using sample-specific string detection in accurate long reads Journal Article
In: Bioinform. Adv., vol. 1, no. 1, 2021, ISSN: 2635-0041.
Abstract | Links | BibTeX | Tags: WP2: Evolutionary/Comparative CPG
@article{Khorsand2021-uq,
title = {Comparative genome analysis using sample-specific string detection in accurate long reads},
author = {Parsoa Khorsand and Luca Denti and Human Genome Structural Variant Consortium and Paola Bonizzoni and Rayan Chikhi and Fereydoun Hormozdiari},
url = {https://github.com/Parsoa/PingPong},
doi = {10.1093/bioadv/vbab005},
issn = {2635-0041},
year = {2021},
date = {2021-05-01},
urldate = {2021-05-01},
journal = {Bioinform. Adv.},
volume = {1},
number = {1},
publisher = {Oxford University Press (OUP)},
abstract = {Comparative genome analysis of two or more whole-genome sequenced (WGS) samples is at the core of most applications in genomics. These include the discovery of genomic differences segregating in populations, case-control analysis in common diseases and diagnosing rare disorders. With the current progress of accurate long-read sequencing technologies (e.g. circular consensus sequencing from PacBio sequencers), we can dive into studying repeat regions of the genome (e.g. segmental duplications) and hard-to-detect variants (e.g. complex structural variants).We propose a novel framework for comparative genome analysis through the discovery of strings that are specific to one genome (‘samples-specific’ strings). We have developed a novel, accurate and efficient computational method for the discovery of sample-specific strings between two groups of WGS samples. The proposed approach will give us the ability to perform comparative genome analysis without the need to map the reads and is not hindered by shortcomings of the reference genome and mapping algorithms. We show that the proposed approach is capable of accurately finding sample-specific strings representing nearly all variation (>98%) reported across pairs or trios of WGS samples using accurate long reads (e.g. PacBio HiFi data).Data, code and instructions for reproducing the results presented in this manuscript are publicly available at https://github.com/Parsoa/PingPong.Supplementary data are available at Bioinformatics Advances online.},
keywords = {WP2: Evolutionary/Comparative CPG},
pubstate = {published},
tppubtype = {article}
}
Comparative genome analysis of two or more whole-genome sequenced (WGS) samples is at the core of most applications in genomics. These include the discovery of genomic differences segregating in populations, case-control analysis in common diseases and diagnosing rare disorders. With the current progress of accurate long-read sequencing technologies (e.g. circular consensus sequencing from PacBio sequencers), we can dive into studying repeat regions of the genome (e.g. segmental duplications) and hard-to-detect variants (e.g. complex structural variants).We propose a novel framework for comparative genome analysis through the discovery of strings that are specific to one genome (‘samples-specific’ strings). We have developed a novel, accurate and efficient computational method for the discovery of sample-specific strings between two groups of WGS samples. The proposed approach will give us the ability to perform comparative genome analysis without the need to map the reads and is not hindered by shortcomings of the reference genome and mapping algorithms. We show that the proposed approach is capable of accurately finding sample-specific strings representing nearly all variation (>98%) reported across pairs or trios of WGS samples using accurate long reads (e.g. PacBio HiFi data).Data, code and instructions for reproducing the results presented in this manuscript are publicly available at https://github.com/Parsoa/PingPong.Supplementary data are available at Bioinformatics Advances online.
22.
Pisanti, Nadia
On-Line Pattern Matching on D-Texts (Invited Talk) Proceedings Article
In: Gawrychowski, Paweł; Starikovskaya, Tatiana (Ed.): 32nd Annual Symposium on Combinatorial Pattern Matching (CPM 2021), pp. 3:1–3:2, Schloss Dagstuhl -- Leibniz-Zentrum für Informatik, Dagstuhl, Germany, 2021, ISSN: 1868-8969.
Abstract | Links | BibTeX | Tags: WP1: Primary CPG, WP2: Evolutionary/Comparative CPG
@inproceedings{Pisanti2021,
title = {On-Line Pattern Matching on D-Texts (Invited Talk)},
author = {Nadia Pisanti},
editor = {Paweł Gawrychowski and Tatiana Starikovskaya},
doi = {10.4230/LIPIcs.CPM.2021.3},
issn = {1868-8969},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
booktitle = {32nd Annual Symposium on Combinatorial Pattern Matching (CPM 2021)},
volume = {191},
pages = {3:1--3:2},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum für Informatik},
address = {Dagstuhl, Germany},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
abstract = {The Elastic Degenerate String Matching (EDSM) problem is defined as that of finding an occurrence of a pattern P of length m in an ED-text T. A D-text (Degenerate text) is a string that actually represents a set of similar and aligned strings (e.g. a pan-genome [The Computational Pan-Genomics Consortium, 2018]) by collapsing common fragments into a standard string, and representing variants with sets of alternative substrings. When such substrings are not bound to have the same size, then we talk about elastic D-strings (ED-strings). In [R.Grossi et al., 2017] we gave an O(nm²+N) time on-line algorithm for EDSM, where n is the length of T and N is its size, defined as the total number of letters. A fundamental toolkit of our algorithm is the O(m²+N) time solution of the later called Active Prefixes problem (AP). In [K.Aoyama et al., 2018], a O(m^{1.5} √{log m}+N) solution for AP was shown, leading to a O(nm^{1.5} √{log m}+N) time solution for EDSM. The natural open problem was thus whether the 1.5 exponent could furtherly be decreased. In [G.Bernardini et al., 2019], we prove several properties that answer this and other questions: we give a conditional O(nm^{1.5}+N) lower bound for EDSM, proving that a combinatorial algorithm solving EDSM in O(nm^{1.5-ε} +N) time would break the Boolean Matrix Multiplication (BMM) conjecture; we use this result as a hint to devise a non-combinatorial algorithm that solves EDSM in O(nm^{1.381}+N) time; we do so by successfully combining Fast Fourier Transform and properties of string periodicity. In my talk I will overview the results above, as well as some interesting side results: the extension to a dictionary rather than a single pattern [S.P.Pissis and A.Retha, 2018], the introduction of errors [G.Bernardini et al., 2020], and a notion of matching among D-strings with its linear time solution [M.Alzamel et al., 2020].},
keywords = {WP1: Primary CPG, WP2: Evolutionary/Comparative CPG},
pubstate = {published},
tppubtype = {inproceedings}
}
The Elastic Degenerate String Matching (EDSM) problem is defined as that of finding an occurrence of a pattern P of length m in an ED-text T. A D-text (Degenerate text) is a string that actually represents a set of similar and aligned strings (e.g. a pan-genome [The Computational Pan-Genomics Consortium, 2018]) by collapsing common fragments into a standard string, and representing variants with sets of alternative substrings. When such substrings are not bound to have the same size, then we talk about elastic D-strings (ED-strings). In [R.Grossi et al., 2017] we gave an O(nm²+N) time on-line algorithm for EDSM, where n is the length of T and N is its size, defined as the total number of letters. A fundamental toolkit of our algorithm is the O(m²+N) time solution of the later called Active Prefixes problem (AP). In [K.Aoyama et al., 2018], a O(m^{1.5} √{log m}+N) solution for AP was shown, leading to a O(nm^{1.5} √{log m}+N) time solution for EDSM. The natural open problem was thus whether the 1.5 exponent could furtherly be decreased. In [G.Bernardini et al., 2019], we prove several properties that answer this and other questions: we give a conditional O(nm^{1.5}+N) lower bound for EDSM, proving that a combinatorial algorithm solving EDSM in O(nm^{1.5-ε} +N) time would break the Boolean Matrix Multiplication (BMM) conjecture; we use this result as a hint to devise a non-combinatorial algorithm that solves EDSM in O(nm^{1.381}+N) time; we do so by successfully combining Fast Fourier Transform and properties of string periodicity. In my talk I will overview the results above, as well as some interesting side results: the extension to a dictionary rather than a single pattern [S.P.Pissis and A.Retha, 2018], the introduction of errors [G.Bernardini et al., 2020], and a notion of matching among D-strings with its linear time solution [M.Alzamel et al., 2020].
23.
Loukides, Grigorios; Pissis, Solon P.
Bidirectional String Anchors: A New String Sampling Mechanism Proceedings Article
In: Mutzel, Petra; Pagh, Rasmus; Herman, Grzegorz (Ed.): 29th Annual European Symposium on Algorithms (ESA 2021), pp. 64:1–64:21, Schloss Dagstuhl -- Leibniz-Zentrum für Informatik, Dagstuhl, Germany, 2021, ISSN: 1868-8969.
Abstract | Links | BibTeX | Tags: WP2: Evolutionary/Comparative CPG
@inproceedings{Loukides2021,
title = {Bidirectional String Anchors: A New String Sampling Mechanism},
author = {Grigorios Loukides and Solon P. Pissis},
editor = {Petra Mutzel and Rasmus Pagh and Grzegorz Herman},
doi = {10.4230/LIPIcs.ESA.2021.64},
issn = {1868-8969},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
booktitle = {29th Annual European Symposium on Algorithms (ESA 2021)},
volume = {204},
pages = {64:1--64:21},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum für Informatik},
address = {Dagstuhl, Germany},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
abstract = { The minimizers sampling mechanism is a popular mechanism for string sampling introduced independently by Schleimer et al. [SIGMOD 2003] and by Roberts et al. [Bioinf. 2004]. Given two positive integers w and k, it selects the lexicographically smallest length-k substring in every fragment of w consecutive length-k substrings (in every sliding window of length w+k-1). Minimizers samples are approximately uniform, locally consistent, and computable in linear time. Although they do not have good worst-case guarantees on their size, they are often small in practice. They thus have been successfully employed in several string processing applications. Two main disadvantages of minimizers sampling mechanisms are: first, they also do not have good guarantees on the expected size of their samples for every combination of w and k; and, second, indexes that are constructed over their samples do not have good worst-case guarantees for on-line pattern searches.
To alleviate these disadvantages, we introduce bidirectional string anchors (bd-anchors), a new string sampling mechanism. Given a positive integer 𝓁, our mechanism selects the lexicographically smallest rotation in every length-𝓁 fragment (in every sliding window of length 𝓁). We show that bd-anchors samples are also approximately uniform, locally consistent, and computable in linear time. In addition, our experiments using several datasets demonstrate that the bd-anchors sample sizes decrease proportionally to 𝓁; and that these sizes are competitive to or smaller than the minimizers sample sizes using the analogous sampling parameters. We provide theoretical justification for these results by analyzing the expected size of bd-anchors samples.
We also show that by using any bd-anchors sample, we can construct, in near-linear time, an index which requires linear (extra) space in the size of the sample and answers on-line pattern searches in near-optimal time. We further show, using several datasets, that a simple implementation of our index is consistently faster for on-line pattern searches than an analogous implementation of a minimizers-based index [Grabowski and Raniszewski, Softw. Pract. Exp. 2017].
Finally, we highlight the applicability of bd-anchors by developing an efficient and effective heuristic for top-K similarity search under edit distance. We show, using synthetic datasets, that our heuristic is more accurate and more than one order of magnitude faster in top-K similarity searches than the state-of-the-art tool for the same purpose [Zhang and Zhang, KDD 2020]. },
keywords = {WP2: Evolutionary/Comparative CPG},
pubstate = {published},
tppubtype = {inproceedings}
}
The minimizers sampling mechanism is a popular mechanism for string sampling introduced independently by Schleimer et al. [SIGMOD 2003] and by Roberts et al. [Bioinf. 2004]. Given two positive integers w and k, it selects the lexicographically smallest length-k substring in every fragment of w consecutive length-k substrings (in every sliding window of length w+k-1). Minimizers samples are approximately uniform, locally consistent, and computable in linear time. Although they do not have good worst-case guarantees on their size, they are often small in practice. They thus have been successfully employed in several string processing applications. Two main disadvantages of minimizers sampling mechanisms are: first, they also do not have good guarantees on the expected size of their samples for every combination of w and k; and, second, indexes that are constructed over their samples do not have good worst-case guarantees for on-line pattern searches.
To alleviate these disadvantages, we introduce bidirectional string anchors (bd-anchors), a new string sampling mechanism. Given a positive integer 𝓁, our mechanism selects the lexicographically smallest rotation in every length-𝓁 fragment (in every sliding window of length 𝓁). We show that bd-anchors samples are also approximately uniform, locally consistent, and computable in linear time. In addition, our experiments using several datasets demonstrate that the bd-anchors sample sizes decrease proportionally to 𝓁; and that these sizes are competitive to or smaller than the minimizers sample sizes using the analogous sampling parameters. We provide theoretical justification for these results by analyzing the expected size of bd-anchors samples.
We also show that by using any bd-anchors sample, we can construct, in near-linear time, an index which requires linear (extra) space in the size of the sample and answers on-line pattern searches in near-optimal time. We further show, using several datasets, that a simple implementation of our index is consistently faster for on-line pattern searches than an analogous implementation of a minimizers-based index [Grabowski and Raniszewski, Softw. Pract. Exp. 2017].
Finally, we highlight the applicability of bd-anchors by developing an efficient and effective heuristic for top-K similarity search under edit distance. We show, using synthetic datasets, that our heuristic is more accurate and more than one order of magnitude faster in top-K similarity searches than the state-of-the-art tool for the same purpose [Zhang and Zhang, KDD 2020].
To alleviate these disadvantages, we introduce bidirectional string anchors (bd-anchors), a new string sampling mechanism. Given a positive integer 𝓁, our mechanism selects the lexicographically smallest rotation in every length-𝓁 fragment (in every sliding window of length 𝓁). We show that bd-anchors samples are also approximately uniform, locally consistent, and computable in linear time. In addition, our experiments using several datasets demonstrate that the bd-anchors sample sizes decrease proportionally to 𝓁; and that these sizes are competitive to or smaller than the minimizers sample sizes using the analogous sampling parameters. We provide theoretical justification for these results by analyzing the expected size of bd-anchors samples.
We also show that by using any bd-anchors sample, we can construct, in near-linear time, an index which requires linear (extra) space in the size of the sample and answers on-line pattern searches in near-optimal time. We further show, using several datasets, that a simple implementation of our index is consistently faster for on-line pattern searches than an analogous implementation of a minimizers-based index [Grabowski and Raniszewski, Softw. Pract. Exp. 2017].
Finally, we highlight the applicability of bd-anchors by developing an efficient and effective heuristic for top-K similarity search under edit distance. We show, using synthetic datasets, that our heuristic is more accurate and more than one order of magnitude faster in top-K similarity searches than the state-of-the-art tool for the same purpose [Zhang and Zhang, KDD 2020].
24.
Charalampopoulos, Panagiotis; Kociumaka, Tomasz; Pissis, Solon P.; Radoszewski, Jakub
Faster Algorithms for Longest Common Substring Proceedings Article
In: Mutzel, Petra; Pagh, Rasmus; Herman, Grzegorz (Ed.): 29th Annual European Symposium on Algorithms (ESA 2021), pp. 30:1–30:17, Schloss Dagstuhl -- Leibniz-Zentrum für Informatik, Dagstuhl, Germany, 2021, ISSN: 1868-8969.
Abstract | Links | BibTeX | Tags: WP2: Evolutionary/Comparative CPG
@inproceedings{Charalampopoulos2021b,
title = {Faster Algorithms for Longest Common Substring},
author = {Panagiotis Charalampopoulos and Tomasz Kociumaka and Solon P. Pissis and Jakub Radoszewski},
editor = {Petra Mutzel and Rasmus Pagh and Grzegorz Herman},
doi = {10.4230/LIPIcs.ESA.2021.30},
issn = {1868-8969},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
booktitle = {29th Annual European Symposium on Algorithms (ESA 2021)},
volume = {204},
pages = {30:1--30:17},
publisher = {Schloss Dagstuhl -- Leibniz-Zentrum für Informatik},
address = {Dagstuhl, Germany},
series = {Leibniz International Proceedings in Informatics (LIPIcs)},
abstract = { In the classic longest common substring (LCS) problem, we are given two strings S and T, each of length at most n, over an alphabet of size σ, and we are asked to find a longest string occurring as a fragment of both S and T. Weiner, in his seminal paper that introduced the suffix tree, presented an 𝒪(n log σ)-time algorithm for this problem [SWAT 1973]. For polynomially-bounded integer alphabets, the linear-time construction of suffix trees by Farach yielded an 𝒪(n)-time algorithm for the LCS problem [FOCS 1997]. However, for small alphabets, this is not necessarily optimal for the LCS problem in the word RAM model of computation, in which the strings can be stored in 𝒪(n log σ/log n) space and read in 𝒪(n log σ/log n) time. We show that, in this model, we can compute an LCS in time 𝒪(n log σ / √{log n}), which is sublinear in n if σ = 2^{o(√{log n})} (in particular, if σ = 𝒪(1)), using optimal space 𝒪(n log σ/log n).
We then lift our ideas to the problem of computing a k-mismatch LCS, which has received considerable attention in recent years. In this problem, the aim is to compute a longest substring of S that occurs in T with at most k mismatches. Flouri et al. showed how to compute a 1-mismatch LCS in 𝒪(n log n) time [IPL 2015]. Thankachan et al. extended this result to computing a k-mismatch LCS in 𝒪(n log^k n) time for k = 𝒪(1) [J. Comput. Biol. 2016]. We show an 𝒪(n log^{k-1/2} n)-time algorithm, for any constant integer k > 0 and irrespective of the alphabet size, using 𝒪(n) space as the previous approaches. We thus notably break through the well-known n log^k n barrier, which stems from a recursive heavy-path decomposition technique that was first introduced in the seminal paper of Cole et al. [STOC 2004] for string indexing with k errors. },
keywords = {WP2: Evolutionary/Comparative CPG},
pubstate = {published},
tppubtype = {inproceedings}
}
In the classic longest common substring (LCS) problem, we are given two strings S and T, each of length at most n, over an alphabet of size σ, and we are asked to find a longest string occurring as a fragment of both S and T. Weiner, in his seminal paper that introduced the suffix tree, presented an 𝒪(n log σ)-time algorithm for this problem [SWAT 1973]. For polynomially-bounded integer alphabets, the linear-time construction of suffix trees by Farach yielded an 𝒪(n)-time algorithm for the LCS problem [FOCS 1997]. However, for small alphabets, this is not necessarily optimal for the LCS problem in the word RAM model of computation, in which the strings can be stored in 𝒪(n log σ/log n) space and read in 𝒪(n log σ/log n) time. We show that, in this model, we can compute an LCS in time 𝒪(n log σ / √{log n}), which is sublinear in n if σ = 2^{o(√{log n})} (in particular, if σ = 𝒪(1)), using optimal space 𝒪(n log σ/log n).
We then lift our ideas to the problem of computing a k-mismatch LCS, which has received considerable attention in recent years. In this problem, the aim is to compute a longest substring of S that occurs in T with at most k mismatches. Flouri et al. showed how to compute a 1-mismatch LCS in 𝒪(n log n) time [IPL 2015]. Thankachan et al. extended this result to computing a k-mismatch LCS in 𝒪(n log^k n) time for k = 𝒪(1) [J. Comput. Biol. 2016]. We show an 𝒪(n log^{k-1/2} n)-time algorithm, for any constant integer k > 0 and irrespective of the alphabet size, using 𝒪(n) space as the previous approaches. We thus notably break through the well-known n log^k n barrier, which stems from a recursive heavy-path decomposition technique that was first introduced in the seminal paper of Cole et al. [STOC 2004] for string indexing with k errors.
We then lift our ideas to the problem of computing a k-mismatch LCS, which has received considerable attention in recent years. In this problem, the aim is to compute a longest substring of S that occurs in T with at most k mismatches. Flouri et al. showed how to compute a 1-mismatch LCS in 𝒪(n log n) time [IPL 2015]. Thankachan et al. extended this result to computing a k-mismatch LCS in 𝒪(n log^k n) time for k = 𝒪(1) [J. Comput. Biol. 2016]. We show an 𝒪(n log^{k-1/2} n)-time algorithm, for any constant integer k > 0 and irrespective of the alphabet size, using 𝒪(n) space as the previous approaches. We thus notably break through the well-known n log^k n barrier, which stems from a recursive heavy-path decomposition technique that was first introduced in the seminal paper of Cole et al. [STOC 2004] for string indexing with k errors.