Dataset Information

CHARTS: a web application for characterizing and comparing tumor subpopulations in publicly available single-cell RNA-seq data sets.

ABSTRACT:

Background

Single-cell RNA-seq (scRNA-seq) enables the profiling of genome-wide gene expression at the single-cell level and in so doing facilitates insight into and information about cellular heterogeneity within a tissue. This is especially important in cancer, where tumor and tumor microenvironment heterogeneity directly impact development, maintenance, and progression of disease. While publicly available scRNA-seq cancer data sets offer unprecedented opportunity to better understand the mechanisms underlying tumor progression, metastasis, drug resistance, and immune evasion, much of the available information has been underutilized, in part, due to the lack of tools available for aggregating and analysing these data.

Results

We present CHARacterizing Tumor Subpopulations (CHARTS), a web application for exploring publicly available scRNA-seq cancer data sets in the NCBI's Gene Expression Omnibus. More specifically, CHARTS enables the exploration of individual gene expression, cell type, malignancy-status, differentially expressed genes, and gene set enrichment results in subpopulations of cells across tumors and data sets. Along with the web application, we also make available the backend computational pipeline that was used to produce the analyses that are available for exploration in the web application.

Conclusion

CHARTS is an easy to use, comprehensive platform for exploring single-cell subpopulations within tumors across the ever-growing collection of public scRNA-seq cancer data sets. CHARTS is freely available at charts.morgridge.org.

SUBMITTER: Bernstein MN

PROVIDER: S-EPMC7903756 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CHARTS: a web application for characterizing and comparing tumor subpopulations in publicly available single-cell RNA-seq data sets.

Bernstein Matthew N MN Ni Zijian Z Collins Michael M Burkard Mark E ME Kendziorski Christina C Stewart Ron R

BMC bioinformatics 20210223 1

<h4>Background</h4>Single-cell RNA-seq (scRNA-seq) enables the profiling of genome-wide gene expression at the single-cell level and in so doing facilitates insight into and information about cellular heterogeneity within a tissue. This is especially important in cancer, where tumor and tumor microenvironment heterogeneity directly impact development, maintenance, and progression of disease. While publicly available scRNA-seq cancer data sets offer unprecedented opportunity to better understand ...[more]

PMID: 33622236

Similar Datasets

Project description:ImportanceThere are limited resources providing postdonation conditions that can occur in living donors (LDs) of solid-organ transplant. Consequently, it is difficult to visualize and understand possible postdonation outcomes in LDs.ObjectiveTo assemble an open access resource that is representative of the demographic characteristics in the US national registry, maintained by the Organ Procurement and Transplantation Network and administered by the United Network for Organ Sharing, but contains more follow-up information to help to examine postdonation outcomes in LDs.Design, setting, and participantsCohort study in which the data for the resource and analyses stemmed from the transplant data set derived from 27 clinical studies from the ImmPort database, which is an open access repository for clinical studies. The studies included data collected from 1963 to 2016. Data from the United Network for Organ Sharing Organ Procurement and Transplantation Network national registry collected from October 1987 to March 2016 were used to determine representativeness. Data analysis took place from June 2016 to May 2018. Data from 20 ImmPort clinical studies (including clinical trials and observational studies) were curated, and a cohort of 11?263 LDs was studied, excluding deceased donors, LDs with 95% or more missing data, and studies without a complete data dictionary. The harmonization process involved the extraction of common features from each clinical study based on categories that included demographic characteristics as well as predonation and postdonation data.Main outcomes and measuresThirty-six postdonation events were identified, represented, and analyzed via a trajectory network analysis.ResultsThe curated data contained 10?869 living kidney donors (median [interquartile range] age, 39 [31-48] years; 6175 [56.8%] women; and 9133 [86.6%] of European descent). A total of 9558 living kidney donors with postdonation data were analyzed. Overall, 1406 LDs (14.7%) had postdonation events. The 4 most common events were hypertension (806 [8.4%]), diabetes (190 [2.0%]), proteinuria (171 [1.8%]), and postoperative ileus (147 [1.5%]). Relatively few events (n?=?269) occurred before the 2-year postdonation mark. Of the 1746 events that took place 2 years or more after donation, 1575 (90.2%) were nonsurgical; nonsurgical conditions tended to occur in the wide range of 2 to 40 years after donation (odds ratio, 38.3; 95% CI, 4.12-1956.9).Conclusions and relevanceMost events that occurred more than 2 years after donation were nonsurgical and could occur up to 40 years after donation. Findings support the construction of a national registry for long-term monitoring of LDs and confirm the value of secondary reanalysis of clinical studies.

Project description:BackgroundThere is an increasing number of interactive web-based advance care planning (ACP) support tools, which are web-based aids in any format encouraging reflection, communication, and processing of publicly available information, most of which cannot be found in the peer-reviewed literature.ObjectiveThis study aims to conduct a systematic review of web-based ACP support tools to describe the characteristics, readability, and quality of content and investigate whether and how they are evaluated.MethodsWe systematically searched the web-based gray literature databases OpenGrey, ClinicalTrials.gov, ProQuest, British Library, Grey Literature in the Netherlands, and Health Services Research Projects in Progress, as well as Google and app stores, and consulted experts using the following eligibility criteria: web-based, designed for the general population, accessible to everyone, interactive (encouraging reflection, communication, and processing of information), and in English or Dutch. The quality of content was evaluated using the Quality Evaluation Scoring Tool (score 0-28-a higher score indicates better quality). To synthesize the characteristics of the ACP tools, readability and quality of content, and whether and how they were evaluated, we used 4 data extraction tables.ResultsA total of 30 tools met the eligibility criteria, including 15 (50%) websites, 10 (33%) web-based portals, 3 (10%) apps, and 2 (7%) with a combination of formats. Of the 30 tools, 24 (80%) mentioned a clear aim, including 7 (23%) that supported reflection or communication, 8 (27%) that supported people in making decisions, 7 (23%) that provided support to document decisions, and 2 (7%) that aimed to achieve all these aims. Of the 30 tools, 7 (23%) provided information on the development, all of which were developed in collaboration with health care professionals, and 3 (10%) with end users. Quality scores ranged between 11 and 28, with most of the lower-scoring tools not referring to information sources.ConclusionsA variety of ACP support tools are available on the web, varying in the quality of content. In the future, users should be involved in the development process of ACP support tools, and the content should be substantiated by scientific evidence.Trial registrationPROSPERO CRD42020184112; https://tinyurl.com/mruf8b43.

Project description:The molecular initiating event for many mechanisms of toxicological action comprise the reactive, covalent binding between an exogenous electrophile and an endogenous nucleophile. The target sites for electrophiles are typically peptides, proteins, enzymes or DNA. Of these, the formation of covalent adducts with proteins and DNA are perhaps the most established as they are most closely associated with skin sensitisation and genotoxicity endpoints. As such, being able to identify electrophilic features within a chemical structure provides a starting point to characterise its reactivity profile. There are a number of software tools that have been developed to help identify structural features indicative of electrophilic reactive potential to address various purposes, including: 1) to facilitate category formation for read-across of toxicity effects such as skin sensitisation potential, as well as 2) to profile substances to identify potential confounding factors to rationalise their activity in high-throughput screening (HTS) assays. Here, three such schemes that have been published in the literature as collections of SMARTS patterns and their associated chemical-biological reaction domains have been compared. The goals are 1) to better understand their scope and coverage, and 2) to assess their performance relative to a published skin sensitisation dataset where manual annotations to assign likely mechanistic domains based on expert judgement were already available. The 3 schemes were then applied to the Tox21 library and the consensus outcome was reported to highlight the proportion of chemicals likely to exhibit a reactivity response, specific to a mechanistic reaction domain, but non-specific with respect to target-tissue based activity. ToxPrint fingerprints were computed and activity enrichments computed to compare the structural features identified for the skin sensitisation dataset and Tox21 chemicals for each 'consensus' reaction domain. Enriched ToxPrints were also used to identify ToxCast assays potentially informative for reactivity.

Project description:Malaria is a deadly disease caused by Apicomplexan parasites of the Plasmodium genus. Several species of the Plasmodium genus are known to be infectious to human, of which P. falciparum is the deadliest. Post-translational modifications (PTMs) of proteins coordinate cell signalling and hence, regulate many biological processes in P. falciparum homeostasis and host infection, of which the most highly studied is phosphorylation. Phosphosites on proteins can be identified by tandem mass spectrometry (MS) performed on enriched samples (phosphoproteomics), followed by downstream computational analyses. We have performed a large-scale meta-analysis of 11 publicly available phosphoproteomics datasets, to build a comprehensive atlas of phosphosites in the P. falciparum proteome, using robust pipelines aimed at strict control of false identifications. We identified a total of 28,495 phosphorylated sites on P. falciparum proteins at 5% false localisation rate (FLR) and, of those, 18,100 at 1% FLR. We identified significant sequence motifs, likely indicative of different groups of kinases, responsible for different groups of phosphosites. Conservation analysis identified clusters of phosphoproteins that are highly conserved, and others that are evolving faster within the Plasmodium genus, and implicated in different pathways. We also explored the structural context of phosphosites, identifying a strong enrichment for phosphosites on fast evolving (low conservation) intrinsically disordered regions (IDRs) of proteins. In other species, IDRs have been shown to have an important role in modulating protein-protein interactions, particularly in signalling, and thus warranting further study for their roles in host-pathogen interactions. All data has made available via UniProt, PRIDE and PeptideAtlas, with visualisation interfaces for exploring phosphosites in the context of other data on Plasmodium proteins.We have re-analysed publicly available mass spectrometry (MS) data sets enriched for phosphopeptides from Asian rice (Oryza sativa). In total we have identified, 15522 phosphosites on Serine, Threonine and Tyrosine residues on rice proteins. The data has been loaded into UniProtKB, enabling researchers to visualise the sites alongside other stored data on rice proteins, including structural models from AlphaFold2, and into PeptideAtlas, enabling visualisation of the source evidence for each site, including scores and source mass spectra. We identified sequence motifs for phosphosites, and link motifs to enrichment of different biological processes, indicating different downstream regulation caused by different kinase groups. We cross-referenced phosphosites against single amino acid variation (SAAV) data sourced from the rice 3000 genomes data, to identify SAAVs within or proximal to phosphosites that could cause loss of a particular site in a given rice variety. The data was further clustered to identify groups of sites with similar patterns across rice family groups, allowing us to identify sites highly conserved in Japonica, but mostly absent in, for example, Aus type rice varieties - known to have different responses to drought. These resources can assist rice researchers to discover alleles with significantly different functional effects across rice varieties.

Dataset Information

CHARTS: a web application for characterizing and comparing tumor subpopulations in publicly available single-cell RNA-seq data sets.

Background

Results

Conclusion

Publications

CHARTS: a web application for characterizing and comparing tumor subpopulations in publicly available single-cell RNA-seq data sets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets