Evidence map›Paper›PMID 32633778›Full record

ArticleNucleic acids research2020

Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring.

Hildreth Robert Frost

Abstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed.

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  13. Gene set optimization for single cell transcriptomics.Computational intelligence methods for bioinformatics and biostatistics : ... international meeting, CIBB ... : revised selected papers. CIBB (Meeting) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author.

Hildreth Robert FrostDepartment of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Zhao - Proj 2P20GM130454 · NIGMS · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 2019 to 2026
$27.2M
Tissue-specific gene set testingK01LM012426 · NLM · DARTMOUTH COLLEGE · PI FROST, HILDRETH · 2016 to 2018
$259k
NCI NIH HHS P30 CA023108NIGMS NIH HHS P20 GM130454NLM NIH HHS K01 LM012426
6 · The paper itself

Abstract

Statistical analysis of single cell RNA-sequencing (scRNA-seq) data is hindered by high levels of technical noise and inflated zero counts. One promising approach for addressing these challenges is gene set testing, or pathway analysis, which can mitigate sparsity and noise, and improve interpretation and power, by aggregating expression data to the pathway level. Unfortunately, methods optimized for bulk transcriptomics perform poorly on scRNA-seq data and progress on single cell-specific techniques has been limited. Importantly, no existing methods support cell-level gene set inference. To address this challenge, we developed a new gene set testing method, Variance-adjusted Mahalanobis (VAM), that integrates with the Seurat framework and can accommodate the technical noise, sparsity and large sample sizes characteristic of scRNA-seq data. The VAM method computes cell-specific pathway scores to transform a cell-by-gene matrix into a cell-by-pathway matrix that can be used for both data visualization and statistical enrichment analysis. Because the distribution of these scores under the null of uncorrelated technical noise has an accurate gamma approximation, both population and cell-level inference is supported. As demonstrated using simulated and real scRNA-seq data, the VAM method provides superior classification accuracy at a lower computation cost relative to existing single sample gene set testing approaches.

Indexed as

AlgorithmsAnimalsCluster AnalysisComputational BiologyGene Expression ProfilingHumansLeukocytes, MononuclearMiceNeurogliaRNARNA-SeqSingle-Cell AnalysisRNA

Identifiers

PMID32633778
PMCPMC7498348

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.