RESUMEN
Haplotype estimation, or phasing, has gained significant traction in large-scale projects due to its valuable contributions to population genetics, variant analysis, and the creation of reference panels for imputation and phasing of new samples. To scale with the growing number of samples, haplotype estimation methods designed for population scale rely on highly optimized statistical models to phase genotype data, and usually ignore read-level information. Statistical methods excel in resolving common variants, however, they still struggle at rare variants due to the lack of statistical information. In this study we introduce SAPPHIRE, a new method that leverages whole-genome sequencing data to enhance the precision of haplotype calls produced by statistical phasing. SAPPHIRE achieves this by refining haplotype estimates through the realignment of sequencing reads, particularly targeting low-confidence phase calls. Our findings demonstrate that SAPPHIRE significantly enhances the accuracy of haplotypes obtained from state of the art methods and also provides the subset of phase calls that are validated by sequencing reads. Finally, we show that our method scales to large data sets by its successful application to the extensive 3.6 Petabytes of sequencing data of the last UK Biobank 200,031 sample release.
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Genética de Población , Haplotipos , Secuenciación Completa del Genoma , Secuenciación Completa del Genoma/métodos , Humanos , Genética de Población/métodos , Genoma Humano , Polimorfismo de Nucleótido Simple/genética , Estudio de Asociación del Genoma Completo/métodos , AlgoritmosRESUMEN
The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.
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Regulación del Desarrollo de la Expresión Génica , Organogénesis/genética , Transcriptoma/genética , Animales , Evolución Biológica , Pollos/genética , Femenino , Humanos , Macaca mulatta/genética , Masculino , Ratones , Zarigüeyas/genética , Conejos , RatasRESUMEN
The fast accumulation of biological data calls for their integration, analysis and exploitation through more systematic approaches. The generation of novel, relevant hypotheses from this enormous quantity of data remains challenging. Logical models have long been used to answer a variety of questions regarding the dynamical behaviours of regulatory networks. As the number of published logical models increases, there is a pressing need for systematic model annotation, referencing and curation in community-supported and standardised formats. This article summarises the key topics and future directions of a meeting entitled 'Annotation and curation of computational models in biology', organised as part of the 2019 [BC]2 conference. The purpose of the meeting was to develop and drive forward a plan towards the standardised annotation of logical models, review and connect various ongoing projects of experts from different communities involved in the modelling and annotation of molecular biological entities, interactions, pathways and models. This article defines a roadmap towards the annotation and curation of logical models, including milestones for best practices and minimum standard requirements.
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Biología Computacional/métodos , Modelos Biológicos , Guías de Práctica Clínica como Asunto , Reproducibilidad de los ResultadosRESUMEN
MOTIVATION: Generation of genotype data has been growing exponentially over the last decade. With the large size of recent datasets comes a storage and computational burden with ever increasing costs. To reduce this burden, we propose XSI, a file format with reduced storage footprint that also allows computation on the compressed data and we show how this can improve future analyses. RESULTS: We show that xSqueezeIt (XSI) allows for a file size reduction of 4-20× compared with compressed BCF and demonstrate its potential for 'compressive genomics' on the UK Biobank whole-genome sequencing genotypes with 8× faster loading times, 5× faster run of homozygozity computation, 30× faster dot products computation and 280× faster allele counts. AVAILABILITY AND IMPLEMENTATION: The XSI file format specifications, API and command line tool are released under open-source (MIT) license and are available at https://github.com/rwk-unil/xSqueezeIt. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Compresión de Datos , Programas Informáticos , Bancos de Muestras Biológicas , Genómica , GenotipoRESUMEN
Direct type I interferon (IFN) signaling on T cells is necessary for the proper expansion, differentiation, and survival of responding T cells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of T cells lacking the type I IFN receptor (Ifnar1(-/-)) remain unclear. We report here that Ifnar1(-/-) T cells were highly susceptible to natural killer (NK) cell-mediated killing in a perforin-dependent manner. Depletion of NK cells prior to lymphocytic choriomeningitis virus (LCMV) infection completely restored the early expansion of Ifnar1(-/-) T cells. Ifnar1(-/-) T cells had elevated expression of natural cytotoxicity triggering receptor 1 (NCR1) ligands upon infection, rendering them targets for NCR1 mediated NK cell attack. Thus, direct sensing of type I IFNs by T cells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which T cells can evade the potent cytotoxic activity of NK cells.
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Antígenos Ly/inmunología , Citotoxicidad Inmunológica , Interferón Tipo I/inmunología , Células Asesinas Naturales/inmunología , Coriomeningitis Linfocítica/inmunología , Receptor 1 Gatillante de la Citotoxidad Natural/inmunología , Receptor de Interferón alfa y beta/genética , Traslado Adoptivo , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Cultivadas , Inmunidad Innata , Activación de Linfocitos/inmunología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Perforina/biosíntesis , Infecciones por Rhabdoviridae/inmunología , Transducción de Señal/inmunología , Vesiculovirus/genética , Vesiculovirus/inmunología , Replicación Viral/inmunologíaRESUMEN
Genetic variations affect behavior and cause disease but understanding how these variants drive complex traits is still an open question. A common approach is to link the genetic variants to intermediate molecular phenotypes such as the transcriptome using RNA-sequencing (RNA-seq). Paradoxically, these variants between the samples are usually ignored at the beginning of RNA-seq analyses of many model organisms. This can skew the transcriptome estimates that are used later for downstream analyses, such as expression quantitative trait locus (eQTL) detection. Here, we assessed the impact of reference-based analysis on the transcriptome and eQTLs in a widely-used mouse genetic population: the BXD panel of recombinant inbred lines. We highlight existing reference bias in the transcriptome data analysis and propose practical solutions which combine available genetic variants, genotypes, and genome reference sequence. The use of custom BXD line references improved downstream analysis compared to classical genome reference. These insights would likely benefit genetic studies with a transcriptomic component and demonstrate that genome references need to be reassessed and improved.
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Sitios de Carácter Cuantitativo , Transcriptoma , Animales , Perfilación de la Expresión Génica , Ratones , Sitios de Carácter Cuantitativo/genética , ARN/genética , Análisis de Secuencia de ARN , Transcriptoma/genéticaRESUMEN
This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples. The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to various depths (up to a 100-fold difference across centers). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignments. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data. The pilot EQA was overall a success. It was able to show the high quality of participating laboratories and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.
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COVID-19 , SARS-CoV-2 , Humanos , Laboratorios , Laboratorios Clínicos , Proyectos PilotoRESUMEN
The timing and duration of sleep results from the interaction between a homeostatic sleep-wake-driven process and a periodic circadian process, and involves changes in gene regulation and expression. Unraveling the contributions of both processes and their interaction to transcriptional and epigenomic regulatory dynamics requires sampling over time under conditions of unperturbed and perturbed sleep. We profiled mRNA expression and chromatin accessibility in the cerebral cortex of mice over a 3-d period, including a 6-h sleep deprivation (SD) on day 2. We used mathematical modeling to integrate time series of mRNA expression data with sleep-wake history, which established that a large proportion of rhythmic genes are governed by the homeostatic process with varying degrees of interaction with the circadian process, sometimes working in opposition. Remarkably, SD caused long-term effects on gene-expression dynamics, outlasting phenotypic recovery, most strikingly illustrated by a damped oscillation of most core clock genes, including Arntl/Bmal1, suggesting that enforced wakefulness directly impacts the molecular clock machinery. Chromatin accessibility proved highly plastic and dynamically affected by SD. Dynamics in distal regions, rather than promoters, correlated with mRNA expression, implying that changes in expression result from constitutively accessible promoters under the influence of enhancers or repressors. Serum response factor (SRF) was predicted as a transcriptional regulator driving immediate response, suggesting that SRF activity mirrors the build-up and release of sleep pressure. Our results demonstrate that a single, short SD has long-term aftereffects at the genomic regulatory level and highlights the importance of the sleep-wake distribution to diurnal rhythmicity and circadian processes.
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Corteza Cerebral/metabolismo , Cromatina/genética , Ritmo Circadiano/genética , Expresión Génica/genética , Sueño/genética , Animales , Epigenómica , Masculino , Ratones , Ratones Endogámicos C57BL , Factor de Respuesta Sérica/metabolismo , Privación de Sueño/genética , Vigilia/genéticaRESUMEN
Whole-exome and targeted sequencing of 13 individuals from 10 unrelated families with overlapping clinical manifestations identified loss-of-function and missense variants in KIAA1109 allowing delineation of an autosomal-recessive multi-system syndrome, which we suggest to name Alkuraya-Kucinskas syndrome (MIM 617822). Shared phenotypic features representing the cardinal characteristics of this syndrome combine brain atrophy with clubfoot and arthrogryposis. Affected individuals present with cerebral parenchymal underdevelopment, ranging from major cerebral parenchymal thinning with lissencephalic aspect to moderate parenchymal rarefaction, severe to mild ventriculomegaly, cerebellar hypoplasia with brainstem dysgenesis, and cardiac and ophthalmologic anomalies, such as microphthalmia and cataract. Severe loss-of-function cases were incompatible with life, whereas those individuals with milder missense variants presented with severe global developmental delay, syndactyly of 2nd and 3rd toes, and severe muscle hypotonia resulting in incapacity to stand without support. Consistent with a causative role for KIAA1109 loss-of-function/hypomorphic variants in this syndrome, knockdowns of the zebrafish orthologous gene resulted in embryos with hydrocephaly and abnormally curved notochords and overall body shape, whereas published knockouts of the fruit fly and mouse orthologous genes resulted in lethality or severe neurological defects reminiscent of the probands' features.
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Artrogriposis/genética , Encéfalo/embriología , Mutación/genética , Proteínas/genética , Adolescente , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Linaje , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
Protein phosphorylation--catalyzed by protein kinases-is the most common post-translational modification. It increases the functional diversity of the proteome and influences various aspects of normal physiology and can be altered in disease states. High throughput profiling of kinases is becoming an essential experimental approach to investigate their activity and this can be achieved using technologies such as PamChip® arrays provided by PamGene for kinase activity measurement. Here, we present 'pamgeneAnalyzeR', an R package developed as an alternative to the manual steps necessary to extract the data from PamChip® peptide microarrays images in a reproducible and robust manner. The extracted data can be directly used for downstream analysis. AVAILABILITY AND IMPLEMENTATION: PamgeneAnalyzeR is implemented in R and can be obtained from https://github.com/amelbek/pamgeneAnalyzeR.
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Proteínas Quinasas , Proteoma , Análisis por Micromatrices , Fosforilación , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Procesamiento Proteico-Postraduccional , Programas InformáticosRESUMEN
MOTIVATION: The potentially low precision associated with the geographic origin of sampled sequences represents an important limitation for spatially explicit (i.e. continuous) phylogeographic inference of fast-evolving pathogens such as RNA viruses. A substantial proportion of publicly available sequences is geo-referenced at broad spatial scale such as the administrative unit of origin, rather than more precise locations (e.g. geographic coordinates). Most frequently, such sequences are either discarded prior to continuous phylogeographic inference or arbitrarily assigned to the geographic coordinates of the centroid of their administrative area of origin for lack of a better alternative. RESULTS: We here implement and describe a new approach that allows to incorporate heterogeneous prior sampling probabilities over a geographic area. External data, such as outbreak locations, are used to specify these prior sampling probabilities over a collection of sub-polygons. We apply this new method to the analysis of highly pathogenic avian influenza H5N1 clade data in the Mekong region. Our method allows to properly include, in continuous phylogeographic analyses, H5N1 sequences that are only associated with large administrative areas of origin and assign them with more accurate locations. Finally, we use continuous phylogeographic reconstructions to analyse the dispersal dynamics of different H5N1 clades and investigate the impact of environmental factors on lineage dispersal velocities. AVAILABILITY AND IMPLEMENTATION: Our new method allowing heterogeneous sampling priors for continuous phylogeographic inference is implemented in the open-source multi-platform software package BEAST 1.10. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Animales , Brotes de Enfermedades , Filogenia , Filogeografía , ProbabilidadRESUMEN
MOTIVATION: To provide high quality computationally tractable enzyme annotation in UniProtKB using Rhea, a comprehensive expert-curated knowledgebase of biochemical reactions which describes reaction participants using the ChEBI (Chemical Entities of Biological Interest) ontology. RESULTS: We replaced existing textual descriptions of biochemical reactions in UniProtKB with their equivalents from Rhea, which is now the standard for annotation of enzymatic reactions in UniProtKB. We developed improved search and query facilities for the UniProt website, REST API and SPARQL endpoint that leverage the chemical structure data, nomenclature and classification that Rhea and ChEBI provide. AVAILABILITY AND IMPLEMENTATION: UniProtKB at https://www.uniprot.org; UniProt REST API at https://www.uniprot.org/help/api; UniProt SPARQL endpoint at https://sparql.uniprot.org/; Rhea at https://www.rhea-db.org.
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Reiformes , Animales , Bases de Datos de Proteínas , Bases del ConocimientoRESUMEN
Sleep is essential for optimal brain functioning and health, but the biological substrates through which sleep delivers these beneficial effects remain largely unknown. We used a systems genetics approach in the BXD genetic reference population (GRP) of mice and assembled a comprehensive experimental knowledge base comprising a deep "sleep-wake" phenome, central and peripheral transcriptomes, and plasma metabolome data, collected under undisturbed baseline conditions and after sleep deprivation (SD). We present analytical tools to interactively interrogate the database, visualize the molecular networks altered by sleep loss, and prioritize candidate genes. We found that a one-time, short disruption of sleep already extensively reshaped the systems genetics landscape by altering 60%-78% of the transcriptomes and the metabolome, with numerous genetic loci affecting the magnitude and direction of change. Systems genetics integrative analyses drawing on all levels of organization imply α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty acid turnover as substrates of the negative effects of insufficient sleep. Our analyses demonstrate that genetic heterogeneity and the effects of insufficient sleep itself on the transcriptome and metabolome are far more widespread than previously reported.
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Ratones Endogámicos/genética , Ratones/genética , Sueño/genética , Animales , Bases de Datos Factuales , Metaboloma/genética , Privación de Sueño/genética , Transcriptoma/genéticaRESUMEN
Rhea (http://www.rhea-db.org) is a comprehensive and non-redundant resource of over 11 000 expert-curated biochemical reactions that uses chemical entities from the ChEBI ontology to represent reaction participants. Originally designed as an annotation vocabulary for the UniProt Knowledgebase (UniProtKB), Rhea also provides reaction data for a range of other core knowledgebases and data repositories including ChEBI and MetaboLights. Here we describe recent developments in Rhea, focusing on a new resource description framework representation of Rhea reaction data and an SPARQL endpoint (https://sparql.rhea-db.org/sparql) that provides access to it. We demonstrate how federated queries that combine the Rhea SPARQL endpoint and other SPARQL endpoints such as that of UniProt can provide improved metabolite annotation and support integrative analyses that link the metabolome through the proteome to the transcriptome and genome. These developments will significantly boost the utility of Rhea as a means to link chemistry and biology for a more holistic understanding of biological systems and their function in health and disease.
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Bases de Datos de Compuestos Químicos , Bases de Datos de Proteínas , Metabolómica/métodos , Programas Informáticos/normas , Humanos , Bases del Conocimiento , Biología de Sistemas/métodosRESUMEN
Cis-Natural Antisense Transcripts (cis-NATs), which overlap protein coding genes and are transcribed from the opposite DNA strand, constitute an important group of noncoding RNAs. Whereas several examples of cis-NATs regulating the expression of their cognate sense gene are known, most cis-NATs function by altering the steady-state level or structure of mRNA via changes in transcription, mRNA stability, or splicing, and very few cases involve the regulation of sense mRNA translation. This study was designed to systematically search for cis-NATs influencing cognate sense mRNA translation in Arabidopsis (Arabidopsis thaliana). Establishment of a pipeline relying on sequencing of total polyA+ and polysomal RNA from Arabidopsis grown under various conditions (i.e. nutrient deprivation and phytohormone treatments) allowed the identification of 14 cis-NATs whose expression correlated either positively or negatively with cognate sense mRNA translation. With use of a combination of cis-NAT stable over-expression in transgenic plants and transient expression in protoplasts, the impact of cis-NAT expression on mRNA translation was confirmed for 4 out of 5 tested cis-NAT:sense mRNA pairs. These results expand the number of cis-NATs known to regulate cognate sense mRNA translation and provide a foundation for future studies of their mode of action. Moreover, this study highlights the role of this class of noncoding RNAs in translation regulation.
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Arabidopsis/genética , Biosíntesis de Proteínas , ARN sin Sentido/genética , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente , ARN Mensajero/genética , ARN de Planta , Reproducibilidad de los Resultados , Análisis de Secuencia de ARN , Factores de Transcripción/genéticaRESUMEN
The Chinese hamster ovary (CHO) cells used to produce biopharmaceutical proteins are known to contain type-C endogenous retrovirus (ERV) sequences in their genome and to release retroviral-like particles. Although evidence for their infectivity is missing, this has raised safety concerns. As the genomic origin of these particles remained unclear, we characterized type-C ERV elements at the genome, transcriptome, and viral particle RNA levels. We identified 173 type-C ERV sequences clustering into three functionally conserved groups. Transcripts from one type-C ERV group were full-length, with intact open reading frames, and cognate viral genome RNA was loaded into retroviral-like particles, suggesting that this ERV group may produce functional viruses. CRISPR-Cas9 genome editing was used to disrupt the gag gene of the expressed type-C ERV group. Comparison of CRISPR-derived mutations at the DNA and RNA level led to the identification of a single ERV as the main source of the release of RNA-loaded viral particles. Clones bearing a Gag loss-of-function mutation in this ERV showed a reduction of RNA-containing viral particle release down to detection limits, without compromising cell growth or therapeutic protein production. Overall, our study provides a strategy to mitigate potential viral particle contaminations resulting from ERVs during biopharmaceutical manufacturing.
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Células CHO/virología , Retrovirus Endógenos , Mutagénesis Sitio-Dirigida/métodos , ARN Viral , Virión/genética , Animales , Sistemas CRISPR-Cas , Cricetinae , Cricetulus , Contaminación de Medicamentos/prevención & control , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Edición Génica , Genoma Viral/genética , Mutación con Pérdida de Función/genética , ARN Viral/genética , ARN Viral/metabolismoRESUMEN
Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of the contribution of proteasome-spliced peptides (PSPs) to the global human leukocyte antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up to 30% of the HLA ligandome. We performed a thorough reanalysis of the reported results using multiple computational tools and various validation steps and concluded that only a fraction of the proposed PSPs passes the quality filters. To better estimate the actual number of PSPs, we present an alternative workflow. We performed de novo sequencing of the HLA-peptide spectra and discarded all de novo sequences found in the UniProt database. We checked whether the remaining de novo sequences could match spliced peptides from human proteins. The spliced sequences were appended to the UniProt fasta file, which was searched by two search tools at a false discovery rate (FDR) of 1%. We find that 2-6% of the HLA ligandome could be explained as spliced protein fragments. The majority of these potential PSPs have good peptide-spectrum match properties and are predicted to bind the respective HLA molecules. However, it remains to be shown how many of these potential PSPs actually originate from proteasomal splicing events.
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Biología Computacional/métodos , Antígenos HLA/metabolismo , Péptidos/genética , Péptidos/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Empalme de Proteína , Presentación de Antígeno/fisiología , Línea Celular Tumoral , Exoma , Humanos , Ligandos , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Proteoma , Transducción de Señal , Espectrometría de Masas en Tándem , Secuenciación del ExomaRESUMEN
Competition for light triggers numerous developmental adaptations known as the "shade-avoidance syndrome" (SAS). Important molecular events underlying specific SAS responses have been identified. However, in natural environments light is often heterogeneous, and it is currently unknown how shading affecting part of a plant leads to local responses. To study this question, we analyzed upwards leaf movement (hyponasty), a rapid adaptation to neighbor proximity, in Arabidopsis We show that manipulation of the light environment at the leaf tip triggers a hyponastic response that is restricted to the treated leaf. This response is mediated by auxin synthesized in the blade and transported to the petiole. Our results suggest that a strong auxin response in the vasculature of the treated leaf and auxin signaling in the epidermis mediate leaf elevation. Moreover, the analysis of an auxin-signaling mutant reveals signaling bifurcation in the control of petiole elongation versus hyponasty. Our work identifies a mechanism for a local shade response that may pertain to other plant adaptations to heterogeneous environments.
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Arabidopsis/fisiología , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/metabolismo , Criptocromos/metabolismo , Regulación de la Expresión Génica de las Plantas , Luz , Mutación , Péptidos/química , Hojas de la Planta/metabolismo , Transducción de SeñalRESUMEN
Achieving high accuracy in orthology inference is essential for many comparative, evolutionary and functional genomic analyses, yet the true evolutionary history of genes is generally unknown and orthologs are used for very different applications across phyla, requiring different precision-recall trade-offs. As a result, it is difficult to assess the performance of orthology inference methods. Here, we present a community effort to establish standards and an automated web-based service to facilitate orthology benchmarking. Using this service, we characterize 15 well-established inference methods and resources on a battery of 20 different benchmarks. Standardized benchmarking provides a way for users to identify the most effective methods for the problem at hand, sets a minimum requirement for new tools and resources, and guides the development of more accurate orthology inference methods.
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Biología Computacional/normas , Genómica/normas , Filogenia , Proteómica/normas , Archaea/clasificación , Archaea/genética , Bacterias/clasificación , Bacterias/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Eucariontes/clasificación , Eucariontes/genética , Ontología de Genes , Genómica/métodos , Modelos Genéticos , Proteómica/métodos , Análisis de Secuencia de Proteína , Homología de Secuencia , Especificidad de la EspecieRESUMEN
In response to neighbor proximity, plants increase the growth of specific organs (e.g., hypocotyls) to enhance access to sunlight. Shade enhances the activity of Phytochrome Interacting Factors (PIFs) by releasing these bHLH transcription factors from phytochrome B-mediated inhibition. PIFs promote elongation by inducing auxin production in cotyledons. In order to elucidate spatiotemporal aspects of the neighbor proximity response, we separately analyzed gene expression patterns in the major light-sensing organ (cotyledons) and in rapidly elongating hypocotyls of Arabidopsis thaliana PIFs initiate transcriptional reprogramming in both organs within 15 min, comprising regulated expression of several early auxin response genes. This suggests that hypocotyl growth is elicited by both local and distal auxin signals. We show that cotyledon-derived auxin is both necessary and sufficient to initiate hypocotyl growth, but we also provide evidence for the functional importance of the local PIF-induced response. With time, the transcriptional response diverges increasingly between organs. We identify genes whose differential expression may underlie organ-specific elongation. Finally, we uncover a growth promotion gene expression signature shared between different developmentally regulated growth processes and responses to the environment in different organs.