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32 Publications visible to you, out of a total of 32
12 Grand Challenges in Single-Cell Data Science

Abstract (Expand)

The recent upswing of microfluidics and combinatorial indexing strategies, further enhanced by very low sequencing costs, have turned single cell sequencing into an empowering technology; analyzing …zing thousands—or even millions—of cells per experimental run is becoming a routine assignment in laboratories worldwide. As a consequence, we are witnessing a data revolution in single cell biology. Although some issues are similar in spirit to those experienced in bulk sequencing, many of the emerging data science problems are unique to single cell analysis; together, they give rise to the new realm of 'Single-Cell Data Science'. Here, we outline twelve challenges that will be central in bringing this new field forward. For each challenge, the current state of the art in terms of prior work is reviewed, and open problems are formulated, with an emphasis on the research goals that motivate them. This compendium is meant to serve as a guideline for established researchers, newcomers and students alike, highlighting interesting and rewarding problems in 'Single-Cell Data Science' for the coming years.

Authors: David Laehnemann, Johannes Köster, Ewa Szczurek, Davis J McCarthy, Stephanie C Hicks, Mark D Robinson, Catalina A Vallejos, Niko Beerenwinkel, Kieran R Campbell, Ahmed Mahfouz, Luca Pinello, Pavel Skums, Alexandros Stamatakis, Camille Stephan-Otto Attolini, Samuel Aparicio, Jasmijn Baaijens, Marleen Balvert, Buys de Barbanson, Antonio Cappuccio, Giacomo Corleone, Bas E Dutilh, Maria Florescu, Victor Guryev, Rens Holmer, Katharina Jahn, Thamar Jessurun Lobo, Emma M Keizer, Indu Khatri, Szymon M Kiełbasa, Jan O Korbel, Alexey M Kozlov, Tzu-Hao Kuo, Boudewijn PF Lelieveldt, Ion I Mandoiu, John C Marioni, Tobias Marschall, Felix Mölder, Amir Niknejad, Łukasz Rączkowski, Marcel Reinders, Jeroen de Ridder, Antoine-Emmanuel Saliba, Antonios Somarakis, Oliver Stegle, Fabian J Theis, Huan Yang, Alex Zelikovsky, Alice C McHardy, Benjamin J Raphael, Sohrab P Shah, Alexander Schönhuth

Date Published: 23rd Aug 2019

Publication Type: Journal

ModelTest-NG: A New and Scalable Tool for the Selection of DNA and Protein Evolutionary Models

Abstract (Expand)

ModelTest-NG is a reimplementation from scratch of jModelTest and ProtTest, two popular tools for selecting the best-fit nucleotide and amino acid substitution models, respectively. ModelTest-NG is one … to two orders of magnitude faster than jModelTest and ProtTest but equally accurate and introduces several new features, such as ascertainment bias correction, mixture, and free-rate models, or the automatic processing of single partitions. ModelTest-NG is available under a GNU GPL3 license at https://github.com/ddarriba/modeltest , last accessed September 2, 2019.

Authors: Diego Darriba, David Posada, Alexey M Kozlov, Alexandros Stamatakis, Benoit Morel, Tomas Flouri

Date Published: 21st Aug 2019

Publication Type: Journal

Using RAxML-NG in Practice

Abstract

Not specified

Authors: Alexey M. Kozlov, Alexandros Stamatakis

Date Published: 6th May 2019

Publication Type: Journal

Long metabarcoding of the eukaryotic rDNA operon to phylogenetically and taxonomically resolve environmental diversity

Abstract (Expand)

High-throughput environmental DNA metabarcoding has revolutionized the analysis of microbial diversity, but this approach is generally restricted to amplicon sizes below 500 base pairs. These short … regions contain limited phylogenetic signal, which makes it impractical to use environmental DNA in full phylogenetic inferences. However, new long-read sequencing technologies such as the Pacific Biosciences platform may provide sufficiently large sequence lengths to overcome the poor phylogenetic resolution of short amplicons. To test this idea, we amplified soil DNA and used PacBio Circular Consensus Sequencing (CCS) to obtain a ~4500 bp region of the eukaryotic rDNA operon spanning most of the small (18S) and large subunit (28S) ribosomal RNA genes. The CCS reads were first treated with a novel curation workflow that generated 650 high-quality OTUs containing the physically linked 18S and 28S regions of the long amplicons. In order to assign taxonomy to these OTUs, we developed a phylogeny-aware approach based on the 18S region that showed greater accuracy and sensitivity than similarity-based and phylogenetic placement-based methods using shorter reads. The taxonomically-annotated OTUs were then combined with available 18S and 28S reference sequences to infer a well-resolved phylogeny spanning all major groups of eukaryotes, allowing to accurately derive the evolutionary origin of environmental diversity. A total of 1019 sequences were included, of which a majority (58%) corresponded to the new long environmental CCS reads. Comparisons to the 18S-only region of our amplicons revealed that the combined 18S-28S genes globally increased the phylogenetic resolution, recovering specific groupings otherwise missing. The long-reads also allowed to directly investigate the relationships among environmental sequences themselves, which represents a key advantage over the placement of short reads on a reference phylogeny. Altogether, our results show that long amplicons can be treated in a full phylogenetic framework to provide greater taxonomic resolution and a robust evolutionary perspective to environmental DNA.

Authors: Mahwash Jamy, Rachel Foster, Pierre Barbera, Lucas Czech, Alexey Kozlov, Alexandros Stamatakis, David Baß, Fabien Burki

Date Published: 5th May 2019

Publication Type: Journal

Models, Optimizations, and Tools for Large-Scale Phylogenetic Inference, Handling Sequence Uncertainty, and Taxonomic Validation

Abstract

Not specified

Author: Alexey Kozlov

Date Published: 2018

Publication Type: Doctoral Thesis

Resolving complex phylogeographic patterns in the Balkan Peninsula using closely related wall-lizard species as a model system

Abstract

Not specified

Authors: Nikolaos Psonis, Aglaia Antoniou, Emmanouela Karameta, Adam D Leaché, Panayiota Kotsakiozi, Diego Darriba, Alexey Kozlov, Alexandros Stamatakis, Dimitris Poursanidis, Oleg Kukushkin, others

Date Published: 2018

Publication Type: Journal

EPA-ng: Massively Parallel Evolutionary Placement of Genetic Sequences

Abstract (Expand)

Next generation sequencing (NGS) technologies have led to a ubiquity of molecular sequence data. This data avalanche is particularly challenging in metagenetics, which focuses on taxonomic identification … of sequences obtained from diverse microbial environments. Phylogenetic placement methods determine how these sequences fit into an evolutionary context. Previous implementations of phylogenetic placement algorithms, such as the evolutionary placement algorithm (EPA) included in RAxML, or PPLACER, are being increasingly used for this purpose. However, due to the steady progress in NGS technologies, the current implementations face substantial scalability limitations. Herein, we present EPA-NG, a complete reimplementation of the EPA that is substantially faster, offers a distributed memory parallelization, and integrates concepts from both, RAxML-EPA and PPLACER. EPA-NG can be executed on standard shared memory, as well as on distributed memory systems (e.g., computing clusters). To demonstrate the scalability of EPA-NG, we placed 1 billion metagenetic reads from the Tara Oceans Project onto a reference tree with 3748 taxa in just under 7 h, using 2048 cores. Our performance assessment shows that EPA-NG outperforms RAxML-EPA and PPLACER by up to a factor of 30 in sequential execution mode, while attaining comparable parallel efficiency on shared memory systems. We further show that the distributed memory parallelization of EPA-NG scales well up to 2048 cores. EPA-NG is available under the AGPLv3 license: https://github.com/Pbdas/epa-ng.

Authors: Pierre Barbera, Alexey M Kozlov, Lucas Czech, Benoit Morel, Diego Darriba, Tomáš Flouri, Alexandros Stamatakis

Date Published: 2018

Publication Type: Journal

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