0000000000207969
AUTHOR
Ana Conesa
The evolution of splicing: transcriptome complexity and transcript distances implemented in TranD
AbstractAlternative splicing contributes to organismal complexity. Comparing transcripts between and within species is an important first step toward understanding questions about how evolution of transcript structure changes between species and contributes to sub-functionalization. These questions are confounded with issues of data quality and availability. The recent explosion of affordable long read sequencing of mRNA has considerably widened the ability to study transcriptional variation in non-model species. In this work, we develop a computational framework that uses nucleotide resolution distance metrics to compare transcript models for structural phenotypes: total transcript length,…
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Additional file 2: Fig. S2. Gene set enrichment analysis (GSEA) for the highest ChIP-exo reads. The genes were ranked according to the number of mapped reads and searched for GO terms enriched at the top of the list in comparison with the rest of the list using GSEA. The resulting list of over-represented GO terms was reduced and visualized with the ReviGO web server ( http://revigo.irb.hr/ ). a) Binding at 25 °C. Left: Results at the Biological Process GO; right: Results at the Cellular Component GO. b) Binding at 37 °C, results are given for the Biological Process GO. The Cellular Component GO gave no results. The size of the circle for each GO term is proportional to the number of genes …
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Additional file 4: Fig. S4. Gene set enrichment analysis (GSEA) analysis of HL ratios (sus1Δ/WT). Gene Ontology (GO) terms (filtered by means of ReviGO software, see Fig, S2) over-represented at the top and at the bottom of the ranked list of HL ratio values.
MOESM5 of The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally
Additional file 5: Table S1. Is a table listing strain used in this study.
MOESM1 of The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally
Additional file 1: Fig. S1. Sus1 occupancy at TFIID-dependent genes was monitored by ChIP analysis of Sus1-TAP in a wild-type strain (Sus1-TAP). As a control, the signal of an isogenic strain bearing no-tagged Sus1 was monitored (No-tag). The occupancy level was calculated as the signal ratio of IP samples in relation to the input signal and relative to an internal control. The resulting normalized ratios were plotted. Error bars represent the SD from at least three independent experiments. Differences in means were assessed by Student’s independent-samples t test. P values
Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis.
Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigen…
Two independent epigenetic biomarkers predict survival in neuroblastoma.
Background Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with a highly variable clinical course, ranging from spontaneous regression to life-threatening disease. Survival rates for high-risk NB patients remain disappointingly low despite multimodal treatment. Thus, there is an urgent clinical need for additional biomarkers to improve risk stratification, treatment management, and survival rates in children with aggressive NB. Results Using gene promoter methylation analysis in 48 neuroblastoma tumors with microarray technology, we found a strong association between survival and gene promoter hypermethylation (P = 0.036). Hypermethylation of 70 genes significantly …
Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome
Context: Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation. Objective: This study aims to investigate the proteome and secretome of in vitro decidualized ESCs. These data were combined with published genomic information and integrated to model the human decidualization interactome. Design: Prospective experimental case–control study. Setting: A private research foundation. Patients: Sixteen healthy volunteer ovum donors. Intervention: Endometrial samples were obtained, and ESCs were isolated and decidualized in vitro. Main Ou…
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Additional file 7. ChIP-exo data analysis.
MOESM3 of The SAGA/TREX-2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally
Additional file 3: Fig. S3. Gene set enrichment analysis (GSEA) of TR ratios (sus1Δ/WT). Gene Ontology (GO) terms (filtered by means of ReviGO software, see Fig, S2) over-represented at the top and at the bottom of the ranked list of TR ratio values.
Identification and visualization of differential isoform expression in RNA-seq time series
Abstract Motivation As sequencing technologies improve their capacity to detect distinct transcripts of the same gene and to address complex experimental designs such as longitudinal studies, there is a need to develop statistical methods for the analysis of isoform expression changes in time series data. Results Iso-maSigPro is a new functionality of the R package maSigPro for transcriptomics time series data analysis. Iso-maSigPro identifies genes with a differential isoform usage across time. The package also includes new clustering and visualization functions that allow grouping of genes with similar expression patterns at the isoform level, as well as those genes with a shift in major …
A Multiomics Study To Unravel the Effects of Developmental Exposure to Endosulfan in Rats: Molecular Explanation for Sex-Dependent Effects
Exposure to low levels of environmental contaminants, including pesticides, induces neurodevelopmental toxicity. Environmental and food contaminants can reach the brain of the fetus, affecting brain development and leading to neurological dysfunction. The pesticide endosulfan is a persistent pollutant, and significant levels still remain detectable in the environment although its use is banned in some countries. In rats, endosulfan exposure during brain development alters motor activity, coordination, learning, and memory, even several months after uptake, and does so in a sex-dependent way. However, the molecular mechanisms driving these effects have not been studied in detail. In this wor…
Understanding disease mechanisms with models of signaling pathway activities
Background Understanding 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. Results Here 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 s…
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Additional file 6: Table S2. Is a table listing Primers for ChIP analysis and RT-qPCR.
Defining the genomic signature of totipotency and pluripotency during early human development.
The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation netw…
Identification and visualisation of differential isoform expression in RNA-seq time series
AbstractAs sequencing technologies improve their capacity to detect distinct transcripts of the same gene and to address complex experimental designs such as longitudinal studies, there is a need to develop statistical methods for the analysis of isoform expression changes in time series data. Iso-maSigPro is a new functionality of the R package maSigPro for transcriptomics time series data analysis. Iso-maSigPro identifies genes with a differential isoform usage across time. The package also includes new clustering and visualization functions that allow grouping of genes with similar expression patterns at the isoform level, as well as those genes with a shift in major expressed isoform. T…
Pathway network inference from gene expression data
[EN] Background: The development of high-throughput omics technologies enabled genome-wide measurements of the activity of cellular elements and provides the analytical resources for the progress of the Systems Biology discipline. Analysis and interpretation of gene expression data has evolved from the gene to the pathway and interaction level, i.e. from the detection of differentially expressed genes, to the establishment of gene interaction networks and the identification of enriched functional categories. Still, the understanding of biological systems requires a further level of analysis that addresses the characterization of the interaction between functional modules. Results: We presen…
tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing
AbstractTraditionally, the functional analysis of gene expression data has used pathway and network enrichment algorithms. These methods are usually gene rather than transcript centric and hence fall short to unravel functional roles associated to posttranscriptional regulatory mechanisms such as Alternative Splicing (AS) and Alternative PolyAdenylation (APA), jointly referred here as Alternative Transcript Processing (AltTP). Moreover, short-read RNA-seq has serious limitations to resolve full-length transcripts, further complicating the study of isoform expression. Recent advances in long-read sequencing open exciting opportunities for studying isoform biology and function. However, there…
The SAGA/TREX‑2 subunit Sus1 binds widely to transcribed genes and affects mRNA turnover globally
Abstract Background Eukaryotic transcription is regulated through two complexes, the general transcription factor IID (TFIID) and the coactivator Spt–Ada–Gcn5 acetyltransferase (SAGA). Recent findings confirm that both TFIID and SAGA contribute to the synthesis of nearly all transcripts and are recruited genome-wide in yeast. However, how this broad recruitment confers selectivity under specific conditions remains an open question. Results Here we find that the SAGA/TREX-2 subunit Sus1 associates with upstream regulatory regions of many yeast genes and that heat shock drastically changes Sus1 binding. While Sus1 binding to TFIID-dominated genes is not affected by temperature, its recruitmen…
Making sense of big data in health research: {T}owards an {EU} action plan
Genome medicine 8(1), 71 (2016). doi:10.1186/s13073-016-0323-y