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1. Seedability: Optimizing alignment parameters for sensitive sequence comparison

Author

Ayad, L.A.K. (Lorraine), Chikhi, R. (Rayan), Pissis, S. (Solon), Ayad, L.A.K. (Lorraine), Chikhi, R. (Rayan), and Pissis, S. (Solon)

Abstract

Motivation: Most sequence alignment techniques make use of exact k-mer hits, called seeds, as anchors to optimize alignment speed. A large number of bioinformatics tools employing seed-based alignment techniques, such as Minimap2, use a single value of k per sequencing technology, without a strong guarantee that this is the best possible value. Given the ubiquity of sequence alignment, identifying values of k that lead to more sensitive alignments is thus an important task. To aid this, we present Seedability, a seed-based alignment framework designed for estimating an optimal seed k-mer length (as well as a minimal number of shared seeds) based on a given alignment identity threshold. In particular, we were motivated to make Minimap2 more sensitive in the pairwise alignment of short sequences. Results: The experimental results herein show improved alignments of short and divergent sequences when using the parameter values determined by Seedability in comparison to the default values of Minimap2. We also show several cases of pairs of real divergent sequences, where the default parameter values of Minimap2 yield no output alignments, but the values output by Seedability produce plausible alignments.

Published
2023
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2. Computational pan-genomics: Status, promises and challenges

Author

Marschall, T. (Tanja), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam M.), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn A.), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul J.P.), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca D.), Cijvat, R. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (E.), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar W.), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John C.), Neerincx, P.B.T. (Pieter B T), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (S.), Raphael, B.J. (Benjamin J.), Reinert, K. (Knut), Ridder, D. (Dick) de, de Ridder, J. (Jeroen), Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley D.), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), Schönhuth, A. (Alexander), Marschall, T. (Tanja), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam M.), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn A.), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul J.P.), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca D.), Cijvat, R. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (E.), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar W.), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John C.), Neerincx, P.B.T. (Pieter B T), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (S.), Raphael, B.J. (Benjamin J.), Reinert, K. (Knut), Ridder, D. (Dick) de, de Ridder, J. (Jeroen), Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley D.), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), and Schönhuth, A. (Alexander)

Abstract

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different Computational methods and paradigms are needed.We will witness the rapid extension of Computational pan-genomics, a new sub-area of research in Computational biology. In this article, we generalize existing definitions and understand a pangenome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a Computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations a

Published
2018
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3. Dualities in tree representations

Author

Chikhi, R. (Rayan), Schönhuth, A. (Alexander), Chikhi, R. (Rayan), and Schönhuth, A. (Alexander)

Abstract

A characterization of the tree T∗ such that BP(T∗) = ↔ DFUDS(T), the reversal of DFUDS(T) is given. An immediate consequence is a rigorous characterization of the tree T such that BP( T^) = DFUDS(T^). In summary, BP and DFUDS are unified within an encompassing framework, which might have the potential to imply future simplifications with regard to queries in BP and/or DFUDS. Immediate benefits displayed here are to identify so far unnoted commonalities in most recent work on the Range Minimum Query problem, and to provide improvements for the Minimum Length Interval Query problem.

Published
2018
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4. Computational pan-genomics: status, promises and challenges

Author

The Computational Pan-Genomics Consortium, Marschall, T. (Tobias), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L.J. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca), Cijvat, C.P. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (Eleazar), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John), Neerincx, P.B.T. (Pieter), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (Sven), Raphael, B.J. (Benjamin), Reinert, K. (Knut), Ridder, D. (Dick) de, Ridder, J. (Jeroen) de, Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L.F.A. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), Schönhuth, A. (Alexander), The Computational Pan-Genomics Consortium, Marschall, T. (Tobias), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L.J. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca), Cijvat, C.P. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (Eleazar), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John), Neerincx, P.B.T. (Pieter), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (Sven), Raphael, B.J. (Benjamin), Reinert, K. (Knut), Ridder, D. (Dick) de, Ridder, J. (Jeroen) de, Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L.F.A. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), and Schönhuth, A. (Alexander)

Abstract

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.

Published
2018
Full Text
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5. Dualities in tree representations

Author

Chikhi, R. (Rayan), Schönhuth, A. (Alexander), Chikhi, R. (Rayan), and Schönhuth, A. (Alexander)

Abstract

A characterization of the tree T∗ such that BP(T∗) = ↔ DFUDS(T), the reversal of DFUDS(T) is given. An immediate consequence is a rigorous characterization of the tree T such that BP( T^) = DFUDS(T^). In summary, BP and DFUDS are unified within an encompassing framework, which might have the potential to imply future simplifications with regard to queries in BP and/or DFUDS. Immediate benefits displayed here are to identify so far unnoted commonalities in most recent work on the Range Minimum Query problem, and to provide improvements for the Minimum Length Interval Query problem.

Published
2018
Full Text
View/download PDF

6. Computational pan-genomics: status, promises and challenges

Author

The Computational Pan-Genomics Consortium, Marschall, T. (Tobias), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L.J. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca), Cijvat, C.P. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (Eleazar), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John), Neerincx, P.B.T. (Pieter), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (Sven), Raphael, B.J. (Benjamin), Reinert, K. (Knut), Ridder, D. (Dick) de, Ridder, J. (Jeroen) de, Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L.F.A. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), Schönhuth, A. (Alexander), The Computational Pan-Genomics Consortium, Marschall, T. (Tobias), Marz, M. (Manja), Abeel, T. (Thomas), Dijkstra, L.J. (Louis), Dutilh, B.E. (Bas), Ghaffaari, A. (Ali), Kersey, P. (Paul), Kloosterman, W.P. (Wigard), Mäkinen, V. (Veli), Novak, A.M. (Adam), Paten, B. (Benedict), Porubsky, D. (David), Rivals, E. (Eric), Alkan, C. (Can), Baaijens, J.A. (Jasmijn), Bakker, P.I.W. (Paul) de, Boeva, V. (Valentina), Bonnal, R.J.P. (Raoul), Chiaromonte, F. (Francesca), Chikhi, R. (Rayan), Ciccarelli, F.D. (Francesca), Cijvat, C.P. (Robin), Datema, E. (Erwin), Duijn, C.M. (Cornelia) van, Eichler, E.E. (Evan), Ernst, C. (Corinna), Eskin, E. (Eleazar), Garrison, E. (Erik), El-Kebir, M. (Mohammed), Klau, G.W. (Gunnar), Korbel, J.O. (Jan), Lameijer, E.-W. (Eric-Wubbo), Langmead, B. (Benjamin), Martin, M. (Marcel), Medvedev, P. (Paul), Mu, J.C. (John), Neerincx, P.B.T. (Pieter), Ouwens, K. (Klaasjan), Peterlongo, P. (Pierre), Pisanti, N. (Nadia), Rahmann, S. (Sven), Raphael, B.J. (Benjamin), Reinert, K. (Knut), Ridder, D. (Dick) de, Ridder, J. (Jeroen) de, Schlesner, M. (Matthias), Schulz-Trieglaff, O. (Ole), Sanders, A.D. (Ashley), Sheikhizadeh, S. (Siavash), Shneider, C. (Carl), Smit, S. (Sandra), Valenzuela, D. (Daniel), Wang, J. (Jiayin), Wessels, L.F.A. (Lodewyk), Zhang, Y. (Ying), Guryev, V. (Victor), Vandin, F. (Fabio), Ye, K. (Kai), and Schönhuth, A. (Alexander)

Abstract

Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.

Published
2018
Full Text
View/download PDF

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