Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis.

ABSTRACT: The effects of confounding factors on gene expression analysis have been extensively studied following the introduction of high-throughput microarrays and subsequently RNA sequencing. In contrast, there is a lack of equivalent analysis and tools for RNA splicing. Here we first assess the effect of confounders on both expression and splicing quantifications in two large public RNA-Seq datasets (TARGET, ENCODE). We show quantification of splicing variations are affected at least as much as those of gene expression, revealing unwanted sources of variations in both datasets. Next, we develop MOCCASIN, a method to correct the effect of both known and unknown confounders on RNA splicing quantification and demonstrate MOCCASIN's effectiveness on both synthetic and real data. Code, synthetic and corrected datasets are all made available as resources.

SUBMITTER: Slaff B

PROVIDER: S-EPMC8184769 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

MOCCASIN: a method for correcting for known and unknown confounders in RNA splicing analysis.

Slaff Barry B Radens Caleb M CM Jewell Paul P Jha Anupama A Lahens Nicholas F NF Grant Gregory R GR Thomas-Tikhonenko Andrei A Lynch Kristen W KW Barash Yoseph Y

Nature communications 20210607 1

The effects of confounding factors on gene expression analysis have been extensively studied following the introduction of high-throughput microarrays and subsequently RNA sequencing. In contrast, there is a lack of equivalent analysis and tools for RNA splicing. Here we first assess the effect of confounders on both expression and splicing quantifications in two large public RNA-Seq datasets (TARGET, ENCODE). We show quantification of splicing variations are affected at least as much as those o ...[more]

PMID: 34099673

Similar Datasets

MOCCASIN: A method for correcting for known and unknown confounders in RNA splicing analysis

Project description:While the effects of confounders on gene expression analysis have been extensively studied there is a lack of equivalent analysis and tools for RNA splicing analysis. Here we assess the effect of confounders in two large public RNA-Seq datasets (TARGET, ENCODE), develop a new method, MOCCASIN, to correct the effect of both known and unknown confounders on RNA splicing quantification, and demonstrate MOCCASIN’s effectiveness on both synthetic and real data.

2020-12-06 | GSE162664 | GEO

Virophages-Known and Unknown Facts.

Project description:The paper presents virophages, which, like their host, giant viruses, are "new" infectious agents whose role in nature, including mammalian health, is important. Virophages, along with their protozoan and algal hosts, are found in fresh inland waters and oceanic and marine waters, including thermal waters and deep-sea vents, as well as in soil, plants, and in humans and animals (ruminants). Representing "superparasitism", almost all of the 39 described virophages (except Zamilon) interact negatively with giant viruses by affecting their replication and morphogenesis and their "adaptive immunity". This causes them to become regulators and, at the same time, defenders of the host of giant viruses protozoa and algae, which are organisms that determine the homeostasis of the aquatic environment. They are classified in the family Lavidaviridae with two genus (Sputnikovirus, Mavirus). However, in 2023, a proposal was presented that they should form the class Maveriviricetes, with four orders and seven families. Their specific structure, including their microsatellite (SSR-Simple Sequence Repeats) and the CVV (cell-virus-virophage, or transpovirion) system described with them, as well as their function, makes them, together with the biological features of giant viruses, form the basis for discussing the existence of a fourth domain in addition to Bacteria, Archaea, and Eukaryota. The paper also presents the hypothetical possibility of using them as a vector for vaccine antigens.

| S-EPMC10301787 | biostudies-literature

MethylResolver-a method for deconvoluting bulk DNA methylation profiles into known and unknown cell contents.

Project description:Bulk tissue DNA methylation profiling has been used to examine epigenetic mechanisms and biomarkers of complex diseases such as cancer. However, heterogeneity of cellular content in tissues complicates result interpretation and utility. In silico deconvolution of cellular fractions from bulk tissue data offers a fast and inexpensive alternative to experimentally measuring such fractions. In this study, we report the design, implementation, and benchmarking of MethylResolver, a Least Trimmed Squares regression-based method for inferring leukocyte subset fractions from methylation profiles of tumor admixtures. Compared to previous approaches MethylResolver is more accurate as unknown cellular content in the mixture increases and is able to resolve tumor purity-scaled immune cell-type fractions without a cancer-specific signature. We also present a pan-cancer deconvolution of TCGA, recapitulating that high eosinophil fraction predicts improved cervical carcinoma survival and identifying elevated B cell fraction as a previously unreported predictor of poor survival for papillary renal cell carcinoma.

| S-EPMC7400544 | biostudies-literature

5-Fluorouracil Cardiotoxicity: Known But Unknown.

Project description: Not available

| S-EPMC8352191 | biostudies-literature

The effect of known and unknown confounders on the relationship between air pollution and Covid-19 mortality in Italy: A sensitivity analysis of an ecological study based on the E-value.

Project description:Back in December 2019, the novel coronavirus disease 2019 (Covid-19) started rapidly spreading worldwide, especially in Italy that was among the most affected countries. The geographical distribution of air pollution and Covid-19 mortality in Italy suggested atmospheric pollution as a worsening factor of severe Covid-19 health outcomes. The present nationwide ecological study focused on all 107 Italian territorial areas, aiming to assess the potential association between Particulate Matter concentration, less than 2.5 μm in diameter (exposure), and Covid-19 mortality rate (outcome) throughout 2020, by looking at 28 potential confounders. A potential positive association between exposure and outcome was observed when performing a multivariate regression analysis with a Negative Binomial model, suggesting that an increase of 1 μg/m3 in the exposure is associated with an increase of 9.0% (95% CI: 6.5%-11.6%) in the average Covid-19 mortality rate, conditional on all 28 potential confounders. A sensitivity analysis, based on the E-value, shows that a hypothetical unmeasured confounder would have to be associated with both PM2.5 concentration and Covid-19 mortality rate by a rate ratio of at least 1.40-fold each to explain away the exposure-outcome association, conditional on all 28 covariates included in the main analysis model. Moreover, the Observed Covariate E-value (OCE) was reported to provide a contextualization of the E-value on the observed covariates included in the study. The OCE sensitivity analysis shows that a set of unknown confounders similar in size and magnitude to the set of the considered climatic factors could potentially explain away the estimated exposure-outcome association. Consequently, the role of climatic factors in the Covid-19 pandemic is worth of further investigation.

| S-EPMC8487852 | biostudies-literature

PMS2 monoallelic mutation carriers: the known unknown.

Project description:Germ-line mutations in MLH1, MSH2, MSH6, and PMS2 have been shown to cause Lynch syndrome. The penetrance of the cancer and tumor spectrum has been repeatedly studied, and multiple professional societies have proposed clinical management guidelines for affected individuals. Several studies have demonstrated a reduced penetrance for monoallelic carriers of PMS2 mutations compared with the other mismatch repair (MMR) genes, but clinical management guidelines have largely proposed the same screening recommendations for all MMR gene carriers. The authors considered whether enough evidence existed to propose new screening guidelines specific to PMS2 mutation carriers with regard to age at onset and frequency of colonic screening. Published reports of PMS2 germ-line mutations were combined with unpublished cases from the authors' research registries and clinical practices, and a discussion of potential modification of cancer screening guidelines was pursued. A total of 234 monoallelic PMS2 mutation carriers from 170 families were included. Approximately 8% of those with colorectal cancer (CRC) were diagnosed before age 30, and each of these tumors presented on the left side of the colon. As it is currently unknown what causes the early onset of CRC in some families with monoallelic PMS2 germline mutations, the authors recommend against reducing cancer surveillance guidelines in families found having monoallelic PMS2 mutations in spite of the reduced penetrance.Genet Med 18 1, 13-19.

| S-EPMC4834863 | biostudies-literature

Germination of Microsporidian Spores: The Known and Unknown.

Project description:Microsporidia are a large group of mysterious obligate intracellular eukaryotic parasites. The microsporidian spore can survive in the absence of nutrients for years under harsh conditions and germinate within seconds under the stimulation of environmental changes like pH and ions. During germination, microsporidia experience an increase in intrasporal osmotic pressure, which leads to an influx of water into the spore, followed by swelling of the polaroplasts and posterior vacuole, which eventually fires the polar filament (PF). Infectious sporoplasm was transported through the extruded polar tube (PT) and delivered into the host cell. Despite much that has been learned about the germination of microsporidia, there are still several major questions that remain unanswered, including: (i) There is still a lack of knowledge about the signaling pathways involved in spore germination. (ii) The germination of spores is not well understood in terms of its specific energetics. (iii) Limited understanding of how spores germinate and how the nucleus and membranes are rearranged during germination. (iv) Only a few proteins in the invasion organelles have been identified; many more are likely undiscovered. This review summarizes the major resolved and unresolved issues concerning the process of microsporidian spore germination.

| S-EPMC10381864 | biostudies-literature

Vitamin C: the known and the unknown and Goldilocks.

Project description:Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful.

| S-EPMC4959991 | biostudies-other

Unifying the known and unknown microbial coding sequence space.

Project description:Genes of unknown function are among the biggest challenges in molecular biology, especially in microbial systems, where 40-60% of the predicted genes are unknown. Despite previous attempts, systematic approaches to include the unknown fraction into analytical workflows are still lacking. Here, we present a conceptual framework, its translation into the computational workflow AGNOSTOS and a demonstration on how we can bridge the known-unknown gap in genomes and metagenomes. By analyzing 415,971,742 genes predicted from 1749 metagenomes and 28,941 bacterial and archaeal genomes, we quantify the extent of the unknown fraction, its diversity, and its relevance across multiple organisms and environments. The unknown sequence space is exceptionally diverse, phylogenetically more conserved than the known fraction and predominantly taxonomically restricted at the species level. From the 71 M genes identified to be of unknown function, we compiled a collection of 283,874 lineage-specific genes of unknown function for Cand. Patescibacteria (also known as Candidate Phyla Radiation, CPR), which provides a significant resource to expand our understanding of their unusual biology. Finally, by identifying a target gene of unknown function for antibiotic resistance, we demonstrate how we can enable the generation of hypotheses that can be used to augment experimental data.

| S-EPMC9132574 | biostudies-literature

Metagenomic profiling of known and unknown microbes with microbeGPS.

Project description:Microbial community profiling identifies and quantifies organisms in metagenomic sequencing data using either reference based or unsupervised approaches. However, current reference based profiling methods only report the presence and abundance of single reference genomes that are available in databases. Since only a small fraction of environmental genomes is represented in genomic databases, these approaches entail the risk of false identifications and often suggest a higher precision than justified by the data. Therefore, we developed MicrobeGPS, a novel metagenomic profiling approach that overcomes these limitations. MicrobeGPS is the first method that identifies microbiota in the sample and estimates their genomic distances to known reference genomes. With this strategy, MicrobeGPS identifies organisms down to the strain level and highlights possibly inaccurate identifications when the correct reference genome is missing. We demonstrate on three metagenomic datasets with different origin that our approach successfully avoids misleading interpretation of results and additionally provides more accurate results than current profiling methods. Our results indicate that MicrobeGPS can enable reference based taxonomic profiling of complex and less characterized microbial communities. MicrobeGPS is open source and available from https://sourceforge.net/projects/microbegps/ as source code and binary distribution for Windows and Linux operating systems.

| S-EPMC4314203 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data