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.
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.
Abstract
Motivation
The reproducibility crisis has highlighted the importance of improving the way bioinformatics data analyses are implemented, executed, and shared. To address this, various tools ...such as content versioning systems, workflow management systems, and software environment management systems have been developed. While these tools are becoming more widely used, there is still much work to be done to increase their adoption. The most effective way to ensure reproducibility becomes a standard part of most bioinformatics data analysis projects is to integrate it into the curriculum of bioinformatics Master’s programs.
Results
In this article, we present the Reprohackathon, a Master’s course that we have been running for the last 3 years at Université Paris-Saclay (France), and that has been attended by a total of 123 students. The course is divided into two parts. The first part includes lessons on the challenges related to reproducibility, content versioning systems, container management, and workflow systems. In the second part, students work on a data analysis project for 3–4 months, reanalyzing data from a previously published study. The Reprohackaton has taught us many valuable lessons, such as the fact that implementing reproducible analyses is a complex and challenging task that requires significant effort. However, providing in-depth teaching of the concepts and the tools during a Master’s degree program greatly improves students’ understanding and abilities in this area.
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.
The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa
. It has since spread to many countries and is expected to rapidly become dominant worldwide. The ...lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development
, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.
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.
Self-assemble-featured Internet of Things Lemoine, Frédéric; Aubonnet, Tatiana; Simoni, Noëmie
Future generation computer systems,
11/2020, Letnik:
112
Journal Article
Recenzirano
Odprti dostop
The Internet of Things supports various industrial applications. The cooperation and coordination of smart things are a promising strategy for satisfying requirements that are beyond the capacity of ...a single smart thing. One of the major challenges for today’s software engineering is the management of large and complex computing systems characterized by a high degree of physical distribution. Examples of such systems arise in many application domains. The number of connected devices grows from billions to hundreds of billions, so a maximum of automatisms must be integrated in IoT architectures in order to control and manage them. Software architects migrate to service oriented architecture and applications are now being constructed as service compositions. Since each IoT device includes one or more microservices, the increasing number of devices around the user makes them difficult to assemble in order to achieve a common goal. In this paper, we propose a self-assembling solution based on self-controlled service components taking into account non-functional requirements concerning the offered quality of services and the structuration of the resulting assembly. Its aim is to build and maintain an assembly of services (taking into account arrival of new peers or failure of existing ones) that, besides functional requirements, also fulfills global quality-of-service and structural requirements.
•Applications are now being constructed as micro-service compositions.•The number of connected devices grows from billions to hundreds of billions.•They have to be controlled and managed.•A maximum of automatisms must be integrated in the IoT architectures.•We introduce a way to automatically assemble a set of IoT device microservices.•They are able to achieve a common goal and react to changes in their execution context.•Our approach can build and maintain an assembly of services.•It also fulfills functional, global QoS and structural requirements.
SARS-CoV-2 is the virus responsible for the global COVID19 pandemic. We review what is known about the origin of this virus, detected in China at the end of December 2019. The genome of this virus ...mainly evolves under the effect of point mutations. These are generally neutral and have no impact on virulence and severity, but some appear to influence infectivity, notably the D614G mutation of the Spike protein. To date (30/09/2020) no recombination of the virus has been documented in the human host, and very few insertions and deletions. The worldwide spread of the virus was the subject of controversies that we summarize, before proposing a new approach free from the limitations of previous methods. The results show a complex scenario with, for example, numerous introductions to the USA and returns of the virus from the USA to certain countries including France.
Activity-dependent transcription has emerged as a major source of gene products that regulate neuronal excitability, connectivity, and synaptic properties. However, the elongation rate of RNA ...polymerases imposes a significant temporal constraint for transcript synthesis, in particular for long genes where new synthesis requires hours. Here we reveal a novel, transcription-independent mechanism that releases transcripts within minutes of neuronal stimulation. We found that, in the mouse neocortex, polyadenylated transcripts retain select introns and are stably accumulated in the cell nucleus. A subset of these intron retention transcripts undergoes activity-dependent splicing, cytoplasmic export, and ribosome loading, thus acutely releasing mRNAs in response to stimulation. This process requires NMDA receptor- and calmodulin-dependent kinase pathways, and it is particularly prevalent for long transcripts. We conclude that regulated intron retention in fully transcribed RNAs represents a mechanism to rapidly mobilize a pool of mRNAs in response to neuronal activity.
•PolyA+ transcripts can stably retain select introns and be confined in the nucleus•Some of these intron-retaining RNAs rapidly undergo splicing upon neuronal activation•Spliced transcripts are exported to the cytosol and loaded onto ribosomes•The activity-dependent intron excision process requires NMDAR and CaMK pathways
Mauger et al. reveal a novel, transcription-independent mechanism to rapidly modify the neuronal transcriptome in response to activity. Neuronal stimulation triggers splicing of transcripts stably retaining select introns, and, thereby, it mobilizes a pool of mRNAs for translation.
With the development of new experimental technologies, biologists are faced with an avalanche of data to be computationally analyzed for scientific advancements and discoveries to emerge. Faced with ...the complexity of analysis pipelines, the large number of computational tools, and the enormous amount of data to manage, there is compelling evidence that many if not most scientific discoveries will not stand the test of time: increasing the reproducibility of computed results is of paramount importance.
The objective we set out in this paper is to place scientific workflows in the context of reproducibility. To do so, we define several kinds of reproducibility that can be reached when scientific workflows are used to perform experiments. We characterize and define the criteria that need to be catered for by reproducibility-friendly scientific workflow systems, and use such criteria to place several representative and widely used workflow systems and companion tools within such a framework. We also discuss the remaining challenges posed by reproducible scientific workflows in the life sciences. Our study was guided by three use cases from the life science domain involving in silico experiments.
•Use cases from the Life Sciences highlighting reproducibility and reuse needs.•Terminology to describe reproducibility levels in scientific workflows.•Criteria to define reproducible-friendly workflow systems and evaluation of systems.•Challenges and opportunities in scientific workflows reproducibility.
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