Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Scaling single-cell genomics from phenomenology to mechanism.

ABSTRACT: Three of the most fundamental questions in biology are how individual cells differentiate to form tissues, how tissues function in a coordinated and flexible fashion and which gene regulatory mechanisms support these processes. Single-cell genomics is opening up new ways to tackle these questions by combining the comprehensive nature of genomics with the microscopic resolution that is required to describe complex multicellular systems. Initial single-cell genomic studies provided a remarkably rich phenomenology of heterogeneous cellular states, but transforming observational studies into models of dynamics and causal mechanisms in tissues poses fresh challenges and requires stronger integration of theoretical, computational and experimental frameworks.

SUBMITTER: Tanay A

PROVIDER: S-EPMC5438464 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Scaling single-cell genomics from phenomenology to mechanism.

Tanay Amos A Regev Aviv A

Nature 20170101 7637

Three of the most fundamental questions in biology are how individual cells differentiate to form tissues, how tissues function in a coordinated and flexible fashion and which gene regulatory mechanisms support these processes. Single-cell genomics is opening up new ways to tackle these questions by combining the comprehensive nature of genomics with the microscopic resolution that is required to describe complex multicellular systems. Initial single-cell genomic studies provided a remarkably ri ...[more]

PMID: 28102262

Similar Datasets

Scaling cross-tissue single-cell annotation models.

Project description:Identifying cellular identities (both novel and well-studied) is one of the key use cases in single-cell transcriptomics. While supervised machine learning has been leveraged to automate cell annotation predictions for some time, there has been relatively little progress both in scaling neural networks to large data sets and in constructing models that generalize well across diverse tissues and biological contexts up to whole organisms. Here, we propose scTab, an automated, feature-attention-based cell type prediction model specific to tabular data, and train it using a novel data augmentation scheme across a large corpus of single-cell RNA-seq observations (22.2 million human cells in total). In addition, scTab leverages deep ensembles for uncertainty quantification. Moreover, we account for ontological relationships between labels in the model evaluation to accommodate for differences in annotation granularity across datasets. On this large-scale corpus, we show that cross-tissue annotation requires nonlinear models and that the performance of scTab scales in terms of training dataset size as well as model size - demonstrating the advantage of scTab over current state-of-the-art linear models in this context. Additionally, we show that the proposed data augmentation schema improves model generalization. In summary, we introduce a de novo cell type prediction model for single-cell RNA-seq data that can be trained across a large-scale collection of curated datasets from a diverse selection of human tissues and demonstrate the benefits of using deep learning methods in this paradigm. Our codebase, training data, and model checkpoints are publicly available at https://github.com/theislab/scTab to further enable rigorous benchmarks of foundation models for single-cell RNA-seq data.

| S-EPMC10592700 | biostudies-literature

Single-Cell Analysis in Cancer Genomics.

Project description:Genetic changes and environmental differences result in cellular heterogeneity among cancer cells within the same tumor, thereby complicating treatment outcomes. Recent advances in single-cell technologies have opened new avenues to characterize the intra-tumor cellular heterogeneity, identify rare cell types, measure mutation rates, and, ultimately, guide diagnosis and treatment. In this paper we review the recent single-cell technological and computational advances at the genomic, transcriptomic, and proteomic levels, and discuss their applications in cancer research.

| S-EPMC5282606 | biostudies-literature

Barcode identification for single cell genomics.

Project description:BackgroundSingle-cell sequencing experiments use short DNA barcode 'tags' to identify reads that originate from the same cell. In order to recover single-cell information from such experiments, reads must be grouped based on their barcode tag, a crucial processing step that precedes other computations. However, this step can be difficult due to high rates of mismatch and deletion errors that can afflict barcodes.ResultsHere we present an approach to identify and error-correct barcodes by traversing the de Bruijn graph of circularized barcode k-mers. Our approach is based on the observation that circularizing a barcode sequence can yield error-free k-mers even when the size of k is large relative to the length of the barcode sequence, a regime which is typical single-cell barcoding applications. This allows for assignment of reads to consensus fingerprints constructed from k-mers.ConclusionWe show that for single-cell RNA-Seq circularization improves the recovery of accurate single-cell transcriptome estimates, especially when there are a high number of errors per read. This approach is robust to the type of error (mismatch, insertion, deletion), as well as to the relative abundances of the cells. Sircel, a software package that implements this approach is described and publically available.

| S-EPMC6337828 | biostudies-literature

Sensitivity to sequencing depth in single-cell cancer genomics.

Project description:Querying cancer genomes at single-cell resolution is expected to provide a powerful framework to understand in detail the dynamics of cancer evolution. However, given the high costs currently associated with single-cell sequencing, together with the inevitable technical noise arising from single-cell genome amplification, cost-effective strategies that maximize the quality of single-cell data are critically needed. Taking advantage of previously published single-cell whole-genome and whole-exome cancer datasets, we studied the impact of sequencing depth and sampling effort towards single-cell variant detection.Five single-cell whole-genome and whole-exome cancer datasets were independently downscaled to 25, 10, 5, and 1× sequencing depth. For each depth level, ten technical replicates were generated, resulting in a total of 6280 single-cell BAM files. The sensitivity of variant detection, including structural and driver mutations, genotyping, clonal inference, and phylogenetic reconstruction to sequencing depth was evaluated using recent tools specifically designed for single-cell data.Altogether, our results suggest that for relatively large sample sizes (25 or more cells) sequencing single tumor cells at depths >?5× does not drastically improve somatic variant discovery, characterization of clonal genotypes, or estimation of single-cell phylogenies.We suggest that sequencing multiple individual tumor cells at a modest depth represents an effective alternative to explore the mutational landscape and clonal evolutionary patterns of cancer genomes.

| S-EPMC5901877 | biostudies-other

The specious art of single-cell genomics.

Project description:Dimensionality reduction is standard practice for filtering noise and identifying relevant features in large-scale data analyses. In biology, single-cell genomics studies typically begin with reduction to 2 or 3 dimensions to produce "all-in-one" visuals of the data that are amenable to the human eye, and these are subsequently used for qualitative and quantitative exploratory analysis. However, there is little theoretical support for this practice, and we show that extreme dimension reduction, from hundreds or thousands of dimensions to 2, inevitably induces significant distortion of high-dimensional datasets. We therefore examine the practical implications of low-dimensional embedding of single-cell data and find that extensive distortions and inconsistent practices make such embeddings counter-productive for exploratory, biological analyses. In lieu of this, we discuss alternative approaches for conducting targeted embedding and feature exploration to enable hypothesis-driven biological discovery.

| S-EPMC10434946 | biostudies-literature

Universal preprocessing of single-cell genomics data.

Project description:We describe a workflow for preprocessing a wide variety of single-cell genomics data types. The approach is based on parsing of machine-readable seqspec assay specifications to customize inputs for kb-python, which uses kallisto and bustools to catalog reads, error correct barcodes, and count reads. The universal preprocessing method is implemented in the Python package cellatlas that is available for download at: https://github.com/cellatlas/cellatlas/.

| S-EPMC10515959 | biostudies-literature

GrandPrix: scaling up the Bayesian GPLVM for single-cell data.

Project description:Motivation:The Gaussian Process Latent Variable Model (GPLVM) is a popular approach for dimensionality reduction of single-cell data and has been used for pseudotime estimation with capture time information. However, current implementations are computationally intensive and will not scale up to modern droplet-based single-cell datasets which routinely profile many tens of thousands of cells. Results:We provide an efficient implementation which allows scaling up this approach to modern single-cell datasets. We also generalize the application of pseudotime inference to cases where there are other sources of variation such as branching dynamics. We apply our method on microarray, nCounter, RNA-seq, qPCR and droplet-based datasets from different organisms. The model converges an order of magnitude faster compared to existing methods whilst achieving similar levels of estimation accuracy. Further, we demonstrate the flexibility of our approach by extending the model to higher-dimensional latent spaces that can be used to simultaneously infer pseudotime and other structure such as branching. Thus, the model has the capability of producing meaningful biological insights about cell ordering as well as cell fate regulation. Availability and implementation:Software available at github.com/ManchesterBioinference/GrandPrix. Supplementary information:Supplementary data are available at Bioinformatics online.

| S-EPMC6298059 | biostudies-literature

Scaling computational genomics to millions of individuals with GPUs.

Project description:Current genomics methods are designed to handle tens to thousands of samples but will need to scale to millions to match the pace of data and hypothesis generation in biomedical science. Here, we show that high efficiency at low cost can be achieved by leveraging general-purpose libraries for computing using graphics processing units (GPUs), such as PyTorch and TensorFlow. We demonstrate > 200-fold decreases in runtime and ~ 5-10-fold reductions in cost relative to CPUs. We anticipate that the accessibility of these libraries will lead to a widespread adoption of GPUs in computational genomics.

| S-EPMC6823959 | biostudies-literature

Scaling up single-cell RNA-seq data analysis with CellBridge workflow.

Project description:SummarySingle-cell RNA sequencing (scRNA-seq) has revolutionized the study of gene expression at the individual cell level, unraveling unprecedented insights into cellular heterogeneity. However, the analysis of scRNA-seq data remains a challenging and time-consuming task, often demanding advanced computational expertise, rendering it impractical for high-volume environments and applications. We present CellBridge, an automated workflow designed to simplify the standard procedures entailed in scRNA-seq data analysis, eliminating the need for specialized computational expertise. CellBridge utilizes state-of-the-art computational methods, integrating a range of advanced functionalities, covering the entire process from raw unaligned sequencing reads to cell type annotation. Hence, CellBridge accelerates the pace of discovery by seamlessly enabling insights into vast volumes of scRNA-seq data, without compromising workflow control and reproducibility.Availability and implementationThe source code, detailed documentation, and materials required to reproduce the results are available on GitHub and archived in Zenodo. For the CellBridge pre-processing step (v1.0.0), access the GitHub repository at https://github.com/Sanofi-Public/PMCB-ToBridge and the Zenodo archive at https://zenodo.org/records/10246161. For the CellBridge processing step (v1.0.0), visit the GitHub repository at https://github.com/Sanofi-Public/PMCB-CellBridge and the Zenodo archive at https://zenodo.org/records/10246046.

| S-EPMC10751228 | biostudies-literature

Resolving medulloblastoma cellular architecture by single-cell genomics.

Project description:Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.

| S-EPMC6754173 | 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