Dataset Information

FITs: forest of imputation trees for recovering true signals in single-cell open chromatin profiles.

ABSTRACT: The advent of single-cell open-chromatin profiling technology has facilitated the analysis of heterogeneity of activity of regulatory regions at single-cell resolution. However, stochasticity and availability of low amount of relevant DNA, cause high drop-out rate and noise in single-cell open-chromatin profiles. We introduce here a robust method called as forest of imputation trees (FITs) to recover original signals from highly sparse and noisy single-cell open-chromatin profiles. FITs makes multiple imputation trees to avoid bias during the restoration of read-count matrices. It resolves the challenging issue of recovering open chromatin signals without blurring out information at genomic sites with cell-type-specific activity. Besides visualization and classification, FITs-based imputation also improved accuracy in the detection of enhancers, calculating pathway enrichment score and prediction of chromatin-interactions. FITs is generalized for wider applicability, especially for highly sparse read-count matrices. The superiority of FITs in recovering signals of minority cells also makes it highly useful for single-cell open-chromatin profile from in vivo samples. The software is freely available at https://reggenlab.github.io/FITs/.

SUBMITTER: Sharma R

PROVIDER: S-EPMC7676476 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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FITs: forest of imputation trees for recovering true signals in single-cell open chromatin profiles.

Sharma Rachesh R Pandey Neetesh N Mongia Aanchal A Mishra Shreya S Majumdar Angshul A Kumar Vibhor V

NAR genomics and bioinformatics 20201119 4

The advent of single-cell open-chromatin profiling technology has facilitated the analysis of heterogeneity of activity of regulatory regions at single-cell resolution. However, stochasticity and availability of low amount of relevant DNA, cause high drop-out rate and noise in single-cell open-chromatin profiles. We introduce here a robust method called as forest of imputation trees (FITs) to recover original signals from highly sparse and noisy single-cell open-chromatin profiles. FITs makes mu ...[more]

PMID: 33575635

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Project description:Background: Single-cell RNA-seq is a powerful tool for measuring gene expression at the resolution of individual cells. A challenge in the analysis of this data is the large amount of zero values, representing either missing data or no expression. Several imputation approaches have been proposed to address this issue, but they generally rely on structure inherent to the dataset under consideration they may not provide any additional information, hence, are limited by the information contained therein and the validity of their assumptions. Methods: We evaluated the risk of generating false positive or irreproducible differential expression when imputing data with six different methods. We applied each method to a variety of simulated datasets as well as to permuted real single-cell RNA-seq datasets and consider the number of false positive gene-gene correlations and differentially expressed genes. Using matched 10X and Smart-seq2 data we examined whether cell-type specific markers were reproducible across datasets derived from the same tissue before and after imputation. Results: The extent of false-positives introduced by imputation varied considerably by method. Data smoothing based methods, MAGIC, knn-smooth and dca, generated many false-positives in both real and simulated data. Model-based imputation methods typically generated fewer false-positives but this varied greatly depending on the diversity of cell-types in the sample. All imputation methods decreased the reproducibility of cell-type specific markers, although this could be mitigated by selecting markers with large effect size and significance. Conclusions: Imputation of single-cell RNA-seq data introduces circularity that can generate false-positive results. Thus, statistical tests applied to imputed data should be treated with care. Additional filtering by effect size can reduce but not fully eliminate these effects. Of the methods we considered, SAVER was the least likely to generate false or irreproducible results, thus should be favoured over alternatives if imputation is necessary.

Dataset Information

FITs: forest of imputation trees for recovering true signals in single-cell open chromatin profiles.

Publications

FITs: forest of imputation trees for recovering true signals in single-cell open chromatin profiles.

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