Objective: To determine the susceptibility of the endometrium to infection by-and thereby potential damage from-SARS-CoV-2. Design: Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. Setting: Infertility research department affiliated with a public hospital. Patient(s): Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. Intervention(s): None. Main Outcome Measure(s): Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. Result(s): Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle. Conclusion(s):Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age. Further, TMPRSS4, along with BSG-mediated viral entry into cells, could imply a susceptible environment for SARS-CoV-2 entry via different mechanisms. Additional studies are warranted to determine the true risk of endometrial infection by SARS-CoV-2 and implications for fertility treatments. (Fertil Steril Ò 2020;114:223-32. Ó2020 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
Motivation: Functional genomics research has expanded enormously in the last decade thanks to the cost reduction in high-throughput technologies and the development of computational tools that generate, standardize and share information on gene and protein function such as the Gene Ontology (GO). Nevertheless, many biologists, especially working with non-model organisms, still suffer from non-existing or low-coverage functional annotation, or simply struggle retrieving, summarizing and querying these data.Results: The Blast2GO Functional Annotation Repository (B2G-FAR) is a bioinformatics resource envisaged to provide functional information for otherwise uncharacterized sequence data and offers data mining tools to analyze a larger repertoire of species than currently available. This new annotation resource has been created by applying the Blast2GO functional annotation engine in a strongly high-throughput manner to the entire space of public available sequences. The resulting repository contains GO term predictions for over 13.2 million non-redundant protein sequences based on BLAST search alignments from the SIMAP database. We generated GO annotation for approximately 150 000 different taxa making available 2000 species with the highest coverage through B2G-FAR. A second section within B2G-FAR holds functional annotations for 17 non-model organism Affymetrix GeneChips.Conclusions: B2G-FAR provides easy access to exhaustive functional annotation for 2000 species offering a good balance between quality and quantity, thereby supporting functional genomics research especially in the case of non-model organisms.Availability: The annotation resource is available at http://www.b2gfar.org.Contact: aconesa@cipf.es; sgoetz@cipf.esSupplementary information: Supplementary data are available at Bioinformatics online.
This research has been funded by IVI-RMA; the authors do not have any competing interests.
BackgroundUnderstanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine.ResultsHere we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation statuses can be interpreted as biomarkers that discriminate among the compared conditions. This type of mechanism-based biomarkers accounts for cell functional activities and can easily be associated to disease or drug action mechanisms. The accuracy of the proposed model is demonstrated with simulations and real datasets.ConclusionsThe proposed model provides detailed information that enables the interpretation disease mechanisms as a consequence of the complex combinations of altered gene expression values. Moreover, it offers a framework for suggesting possible ways of therapeutic intervention in a pathologically perturbed system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-014-0121-3) contains supplementary material, which is available to authorized users.
Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism-based biomarkers which provide insight into or drug molecular mechanisms of action (MoA).
Signaling pathways constitute a valuable source of information that allows interpreting the way in which alterations in gene activities affect to particular cell functionalities. There are web tools available that allow viewing and editing pathways, as well as representing experimental data on them. However, few methods aimed to identify the signaling circuits, within a pathway, associated to the biological problem studied exist and none of them provide a convenient graphical web interface. We present PATHiWAYS, a web-based signaling pathway visualization system that infers changes in signaling that affect cell functionality from the measurements of gene expression values in typical expression microarray case–control experiments. A simple probabilistic model of the pathway is used to estimate the probabilities for signal transmission from any receptor to any final effector molecule (taking into account the pathway topology) using for this the individual probabilities of gene product presence/absence inferred from gene expression values. Significant changes in these probabilities allow linking different cell functionalities triggered by the pathway to the biological problem studied. PATHiWAYS is available at: http://pathiways.babelomics.org/.
BackgroundSerrated adenocarcinoma (SAC) is a recently recognized colorectal cancer (CRC) subtype accounting for 7.5–8.7 % of CRCs. It has been shown that SAC has a worse prognosis and different histological and molecular features compared to conventional carcinoma (CC) but, to date, there is no study analysing its methylome profile.ResultsThe methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 103 colorectal specimens, including 39 SACs and 34 matched CCs, from Spanish and Finnish patients. Microarray data showed a higher representation of morphogenesis-, neurogenesis-, cytoskeleton- and vesicle transport-related functions and also significant differential methylation of 15 genes, including the iodothyronine deiodinase DIO3 and the forkhead family transcription factor FOXD2 genes which were validated at the CpG, mRNA and protein level using pyrosequencing, methylation-specific PCR, quantitative polymerase chain reaction (qPCR) and immunohistochemistry. A quantification study of the methylation status of CpG sequences in FOXD2 demonstrated a novel region controlling gene expression. Moreover, differences in these markers were also evident when comparing SAC with CRC showing molecular and histological features of high-level microsatellite instability.ConclusionsThis methylome study demonstrates distinct epigenetic regulation patterns in SAC which are consistent to previous expression profile studies and that DIO3 and FOXD2 might be molecular targets for a specific histology-oriented treatment of CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0128-7) contains supplementary material, which is available to authorized users.
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