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Book ; Conference proceedings: Bioinformatics of African pathogens and vectors

Gascuel, Olivier

Nairobi, Kenya, 28th May - 2nd June 2007

(Infection, genetics and evolution ; 9,3 = Special issue)

2009

Event/congress	Bioinformatics of African Pathogens and Vectors Conference (2007, Nairobi)
Author's details	Bioinformatics of African Pathogens and Vectors Conference. Guest ed.: Oliver Gascuel
Series title	Infection, genetics and evolution ; 9,3 = Special issue
Collection
Language	English
Size	S. 305 - 386 : Ill., graph. Darst.
Publisher	Elsevier
Publishing place	Amsterdam u.a.
Publishing country	Netherlands
Document type	Book ; Conference proceedings
Note	Enth. auch: Abstracts
HBZ-ID	HT015939905
Database	Catalogue ZB MED Medicine, Health

In stock of ZB MED Cologne/Königswinter

Shelf mark	Loan status	Location
Zs A 5645 -9-	not available for loan	Zeitschriften-Lesesaal

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Article ; Online: Accurate Detection of Convergent Mutations in Large Protein Alignments With ConDor.

Morel, Marie / Zhukova, Anna / Lemoine, Frédéric / Gascuel, Olivier

Genome biology and evolution

2024 Volume 16, Issue 4

Abstract: Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in ... ...

Abstract	Evolutionary convergences are observed at all levels, from phenotype to DNA and protein sequences, and changes at these different levels tend to be correlated. Notably, convergent mutations can lead to convergent changes in phenotype, such as changes in metabolism, drug resistance, and other adaptations to changing environments. We propose a two-component approach to detect mutations subject to convergent evolution in protein alignments. The "Emergence" component selects mutations that emerge more often than expected, while the "Correlation" component selects mutations that correlate with the convergent phenotype under study. With regard to Emergence, a phylogeny deduced from the alignment is provided by the user and is used to simulate the evolution of each alignment position. These simulations allow us to estimate the expected number of mutations in a neutral model, which is compared to the observed number of mutations in the data studied. In Correlation, a comparative phylogenetic approach, is used to measure whether the presence of each of the observed mutations is correlated with the convergent phenotype. Each component can be used on its own, for example Emergence when no phenotype is available. Our method is implemented in a standalone workflow and a webserver, called ConDor. We evaluate the properties of ConDor using simulated data, and we apply it to three real datasets: sedge PEPC proteins, HIV reverse transcriptase, and fish rhodopsin. The results show that the two components of ConDor complement each other, with an overall accuracy that compares favorably to other available tools, especially on large datasets.
MeSH term(s)	Animals ; Phylogeny ; Evolution, Molecular ; Fishes/genetics ; Rhodopsin/genetics ; Mutation
Chemical Substances	Rhodopsin (9009-81-8)
Language	English
Publishing date	2024-03-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evae040
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Article ; Online: Modeling Drug Resistance Emergence and Transmission in HIV-1 in the UK.

Zhukova, Anna / Dunn, David / Gascuel, Olivier

Viruses

2023 Volume 15, Issue 6

Abstract: A deeper understanding of HIV-1 transmission and drug resistance mechanisms can lead to improvements in current treatment policies. However, the rates at which HIV-1 drug resistance mutations (DRMs) are acquired and which transmitted DRMs persist are ... ...

Abstract	A deeper understanding of HIV-1 transmission and drug resistance mechanisms can lead to improvements in current treatment policies. However, the rates at which HIV-1 drug resistance mutations (DRMs) are acquired and which transmitted DRMs persist are multi-factorial and vary considerably between different mutations. We develop a method for the estimation of drug resistance acquisition and transmission patterns. The method uses maximum likelihood ancestral character reconstruction informed by treatment roll-out dates and allows for the analysis of very large datasets. We apply our method to transmission trees reconstructed on the data obtained from the UK HIV Drug Resistance Database to make predictions for known DRMs. Our results show important differences between DRMs, in particular between polymorphic and non-polymorphic DRMs and between the B and C subtypes. Our estimates of reversion times, based on a very large number of sequences, are compatible but more accurate than those already available in the literature, with narrower confidence intervals. We consistently find that large resistance clusters are associated with polymorphic DRMs and DRMs with long loss times, which require special surveillance. As in other high-income countries (e.g., Switzerland), the prevalence of sequences with DRMs is decreasing, but among these, the fraction of transmitted resistance is clearly increasing compared to the fraction of acquired resistance mutations. All this indicates that efforts to monitor these mutations and the emergence of resistance clusters in the population must be maintained in the long term.
MeSH term(s)	Humans ; HIV-1/genetics ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; Drug Resistance, Viral/genetics ; Genotype ; Mutation ; HIV Seropositivity ; United Kingdom/epidemiology ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2023-05-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15061244
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Article ; Online: Robustness of Felsenstein's Versus Transfer Bootstrap Supports With Respect to Taxon Sampling.

Zaharias, Paul / Lemoine, Frédéric / Gascuel, Olivier

Systematic biology

2023 Volume 72, Issue 6, Page(s) 1280–1295

Abstract: The bootstrap method is based on resampling sequence alignments and re-estimating trees. Felsenstein's bootstrap proportions (FBP) are the most common approach to assess the reliability and robustness of sequence-based phylogenies. However, when ... ...

Abstract	The bootstrap method is based on resampling sequence alignments and re-estimating trees. Felsenstein's bootstrap proportions (FBP) are the most common approach to assess the reliability and robustness of sequence-based phylogenies. However, when increasing taxon sampling (i.e., the number of sequences) to hundreds or thousands of taxa, FBP tend to return low support for deep branches. The transfer bootstrap expectation (TBE) has been recently suggested as an alternative to FBP. TBE is measured using a continuous transfer index in [0,1] for each bootstrap tree, instead of the binary {0,1} index used in FBP to measure the presence/absence of the branch of interest. TBE has been shown to yield higher and more informative supports while inducing a very low number of falsely supported branches. Nonetheless, it has been argued that TBE must be used with care due to sampling issues, especially in datasets with a high number of closely related taxa. In this study, we conduct multiple experiments by varying taxon sampling and comparing FBP and TBE support values on different phylogenetic depths, using empirical datasets. Our results show that the main critique of TBE stands in extreme cases with shallow branches and highly unbalanced sampling among clades, but that TBE is still robust in most cases, while FBP is inescapably negatively impacted by high taxon sampling. We suggest guidelines and good practices in TBE (and FBP) computing and interpretation.
MeSH term(s)	Phylogeny ; Reproducibility of Results
Language	English
Publishing date	2023-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1482572-7
ISSN	1076-836X ; 1063-5157
ISSN (online)	1076-836X
ISSN	1063-5157
DOI	10.1093/sysbio/syad052
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Article ; Online: Fast and Accurate Maximum-Likelihood Estimation of Multi-Type Birth-Death Epidemiological Models from Phylogenetic Trees.

Zhukova, Anna / Hecht, Frédéric / Maday, Yvon / Gascuel, Olivier

Systematic biology

2023 Volume 72, Issue 6, Page(s) 1387–1402

Abstract: Multi-type birth-death (MTBD) models are phylodynamic analogies of compartmental models in classical epidemiology. They serve to infer such epidemiological parameters as the average number of secondary infections Re and the infectious time from a ... ...

Abstract	Multi-type birth-death (MTBD) models are phylodynamic analogies of compartmental models in classical epidemiology. They serve to infer such epidemiological parameters as the average number of secondary infections Re and the infectious time from a phylogenetic tree (a genealogy of pathogen sequences). The representatives of this model family focus on various aspects of pathogen epidemics. For instance, the birth-death exposed-infectious (BDEI) model describes the transmission of pathogens featuring an incubation period (when there is a delay between the moment of infection and becoming infectious, as for Ebola and SARS-CoV-2), and permits its estimation along with other parameters. With constantly growing sequencing data, MTBD models should be extremely useful for unravelling information on pathogen epidemics. However, existing implementations of these models in a phylodynamic framework have not yet caught up with the sequencing speed. Computing time and numerical instability issues limit their applicability to medium data sets (≤ 500 samples), while the accuracy of estimations should increase with more data. We propose a new highly parallelizable formulation of ordinary differential equations for MTBD models. We also extend them to forests to represent situations when a (sub-)epidemic started from several cases (e.g., multiple introductions to a country). We implemented it for the BDEI model in a maximum likelihood framework using a combination of numerical analysis methods for efficient equation resolution. Our implementation estimates epidemiological parameter values and their confidence intervals in two minutes on a phylogenetic tree of 10,000 samples. Comparison to the existing implementations on simulated data shows that it is not only much faster but also more accurate. An application of our tool to the 2014 Ebola epidemic in Sierra-Leone is also convincing, with very fast calculation and precise estimates. As MTBD models are closely related to Cladogenetic State Speciation and Extinction (ClaSSE)-like models, our findings could also be easily transferred to the macroevolution domain.
MeSH term(s)	Humans ; Phylogeny ; Hemorrhagic Fever, Ebola/epidemiology ; Likelihood Functions ; Epidemiological Models ; Epidemics
Language	English
Publishing date	2023-09-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1482572-7
ISSN	1076-836X ; 1063-5157
ISSN (online)	1076-836X
ISSN	1063-5157
DOI	10.1093/sysbio/syad059
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Article ; Online: Correction to 'Gotree/Goalign: toolkit and Go API to facilitate the development of phylogenetic workflows'.

Lemoine, Frédéric / Gascuel, Olivier

NAR genomics and bioinformatics

2021 Volume 3, Issue 3, Page(s) lqab083

Abstract: This corrects the article DOI: 10.1093/nargab/lqab075.]. ...

Abstract	[This corrects the article DOI: 10.1093/nargab/lqab075.].
Language	English
Publishing date	2021-09-10
Publishing country	England
Document type	Published Erratum
ISSN	2631-9268
ISSN (online)	2631-9268
DOI	10.1093/nargab/lqab083
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Article ; Online: Gotree/Goalign: toolkit and Go API to facilitate the development of phylogenetic workflows.

Lemoine, Frédéric / Gascuel, Olivier

NAR genomics and bioinformatics

2021 Volume 3, Issue 3, Page(s) lqab075

Abstract: Phylogenetics is nowadays at the center of numerous studies in many fields, ranging from comparative genomics to molecular epidemiology. However, phylogenetic analysis workflows are usually complex and difficult to implement, as they are often composed ... ...

Abstract	Phylogenetics is nowadays at the center of numerous studies in many fields, ranging from comparative genomics to molecular epidemiology. However, phylogenetic analysis workflows are usually complex and difficult to implement, as they are often composed of many small, reccuring, but important data manipulations steps. Among these, we can find file reformatting, sequence renaming, tree re-rooting, tree comparison, bootstrap support computation, etc. These are often performed by custom scripts or by several heterogeneous tools, which may be error prone, uneasy to maintain and produce results that are challenging to reproduce. For all these reasons, the development and reuse of phylogenetic workflows is often a complex task. We identified many operations that are part of most phylogenetic analyses, and implemented them in a toolkit called Gotree/Goalign. The Gotree/Goalign toolkit implements more than 120 user-friendly commands and an API dedicated to multiple sequence alignment and phylogenetic tree manipulations. It is developed in Go, which makes executables easily installable, integrable in workflow environments, and parallelizable when possible. Moreover, Go is a compiled language, which accelerates computations compared to interpreted languages. This toolkit is freely available on most platforms (Linux, MacOS and Windows) and most architectures (amd64, i386) on GitHub at https://github.com/evolbioinfo/gotree, Bioconda and DockerHub.
Language	English
Publishing date	2021-08-11
Publishing country	England
Document type	Journal Article
ISSN	2631-9268
ISSN (online)	2631-9268
DOI	10.1093/nargab/lqab075
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Darwinian Uncertainty Principle.

Gascuel, Olivier / Steel, Mike

Systematic biology

2019 Volume 69, Issue 3, Page(s) 521–529

Abstract: Reconstructing ancestral characters and traits along a phylogenetic tree is central to evolutionary biology. It is the key to understanding morphology changes among species, inferring ancestral biochemical properties of life, or recovering migration ... ...

Abstract	Reconstructing ancestral characters and traits along a phylogenetic tree is central to evolutionary biology. It is the key to understanding morphology changes among species, inferring ancestral biochemical properties of life, or recovering migration routes in phylogeography. The goal is 2-fold: to reconstruct the character state at the tree root (e.g., the region of origin of some species) and to understand the process of state changes along the tree (e.g., species flow between countries). We deal here with discrete characters, which are "unique," as opposed to sequence characters (nucleotides or amino-acids), where we assume the same model for all the characters (or for large classes of characters with site-dependent models) and thus benefit from multiple information sources. In this framework, we use mathematics and simulations to demonstrate that although each goal can be achieved with high accuracy individually, it is generally impossible to accurately estimate both the root state and the rates of state changes along the tree branches, from the observed data at the tips of the tree. This is because the global rates of state changes along the branches that are optimal for the two estimation tasks have opposite trends, leading to a fundamental trade-off in accuracy. This inherent "Darwinian uncertainty principle" concerning the simultaneous estimation of "patterns" and "processes" governs ancestral reconstructions in biology. For certain tree shapes (typically speciation trees) the uncertainty of simultaneous estimation is reduced when more tips are present; however, for other tree shapes it does not (e.g., coalescent trees used in population genetics).
MeSH term(s)	Classification/methods ; Computer Simulation ; Models, Theoretical ; Phylogeny
Language	English
Publishing date	2019-08-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1482572-7
ISSN	1076-836X ; 1063-5157
ISSN (online)	1076-836X
ISSN	1063-5157
DOI	10.1093/sysbio/syz054
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Article ; Online: Measuring Phylogenetic Information of Incomplete Sequence Data.

Seo, Tae-Kun / Gascuel, Olivier / Thorne, Jeffrey L

Systematic biology

2021 Volume 71, Issue 3, Page(s) 630–648

Abstract: Widely used approaches for extracting phylogenetic information from aligned sets of molecular sequences rely upon probabilistic models of nucleotide substitution or amino-acid replacement. The phylogenetic information that can be extracted depends on the ...

Abstract	Widely used approaches for extracting phylogenetic information from aligned sets of molecular sequences rely upon probabilistic models of nucleotide substitution or amino-acid replacement. The phylogenetic information that can be extracted depends on the number of columns in the sequence alignment and will be decreased when the alignment contains gaps due to insertion or deletion events. Motivated by the measurement of information loss, we suggest assessment of the effective sequence length (ESL) of an aligned data set. The ESL can differ from the actual number of columns in a sequence alignment because of the presence of alignment gaps. Furthermore, the estimation of phylogenetic information is affected by model misspecification. Inevitably, the actual process of molecular evolution differs from the probabilistic models employed to describe this process. This disparity means the amount of phylogenetic information in an actual sequence alignment will differ from the amount in a simulated data set of equal size, which motivated us to develop a new test for model adequacy. Via theory and empirical data analysis, we show how to disentangle the effects of gaps and model misspecification. By comparing the Fisher information of actual and simulated sequences, we identify which alignment sites and tree branches are most affected by gaps and model misspecification. [Fisher information; gaps; insertion; deletion; indel; model adequacy; goodness-of-fit test; sequence alignment.].
MeSH term(s)	Evolution, Molecular ; INDEL Mutation ; Models, Genetic ; Models, Statistical ; Phylogeny ; Sequence Alignment
Language	English
Publishing date	2021-09-01
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1482572-7
ISSN	1076-836X ; 1063-5157
ISSN (online)	1076-836X
ISSN	1063-5157
DOI	10.1093/sysbio/syab073
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Article ; Online: COVID-Align: accurate online alignment of hCoV-19 genomes using a profile HMM.

Lemoine, Frédéric / Blassel, Luc / Voznica, Jakub / Gascuel, Olivier

Bioinformatics (Oxford, England)

2020 Volume 37, Issue 12, Page(s) 1761–1762

Abstract: Motivation: The first cases of the COVID-19 pandemic emerged in December 2019. Until the end of February 2020, the number of available genomes was below 1000 and their multiple alignment was easily achieved using standard approaches. Subsequently, the ... ...

Abstract	Motivation: The first cases of the COVID-19 pandemic emerged in December 2019. Until the end of February 2020, the number of available genomes was below 1000 and their multiple alignment was easily achieved using standard approaches. Subsequently, the availability of genomes has grown dramatically. Moreover, some genomes are of low quality with sequencing/assembly errors, making accurate re-alignment of all genomes nearly impossible on a daily basis. A more efficient, yet accurate approach was clearly required to pursue all subsequent bioinformatics analyses of this crucial data. Results: hCoV-19 genomes are highly conserved, with very few indels and no recombination. This makes the profile HMM approach particularly well suited to align new genomes, add them to an existing alignment and filter problematic ones. Using a core of ∼2500 high quality genomes, we estimated a profile using HMMER, and implemented this profile in COVID-Align, a user-friendly interface to be used online or as standalone via Docker. The alignment of 1000 genomes requires ∼50 minutes on our cluster. Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels). Availability and implementation: https://covalign.pasteur.cloud, hub.docker.com/r/evolbioinfo/covid-align. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	COVID-19 ; Genome ; Humans ; Pandemics ; SARS-CoV-2 ; Software
Keywords	covid19
Language	English
Publishing date	2020-10-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btaa871
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