Evidence map›Paper›PMID 33708217›Full record

ArticleFrontiers in immunology2021

Single Cell RNA-Seq and Machine Learning Reveal Novel Subpopulations in Low-Grade Inflammatory Monocytes With Unique Regulatory Circuits.

Jiyoung Lee, Shuo Geng, Song Li, Liwu Li

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
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

16 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  3. CCR2Cellular & molecular immunology · 2025
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  9. Comparative analyses of monocyte memory dynamics from mice to humans.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  10. Article
  11. Article
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  14. Monocyte programming by cancer therapy.Frontiers in immunology · 2022
    Review
  15. Article
  16. Article
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

4 authors at 1 institution in 1 country.

Jiyoung LeePh.D. Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Shuo GengDepartment of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Song LiPh.D. Program in Genetics, Bioinformatics and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Liwu LiDepartment of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
Virginia Tech · US

Funding

Modulation of innate immune cellular homeostasis and inflammation resolutionR01HL115835 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI LI, LIWU · 2012 to 2021
$3.6M
NHLBI NIH HHS R01 HL115835
6 · The paper itself

Abstract

Subclinical doses of LPS (SD-LPS) are known to cause low-grade inflammatory activation of monocytes, which could lead to inflammatory diseases including atherosclerosis and metabolic syndrome. Sodium 4-phenylbutyrate is a potential therapeutic compound which can reduce the inflammation caused by SD-LPS. To understand the gene regulatory networks of these processes, we have generated scRNA-seq data from mouse monocytes treated with these compounds and identified 11 novel cell clusters. We have developed a machine learning method to integrate scRNA-seq, ATAC-seq, and binding motifs to characterize gene regulatory networks underlying these cell clusters. Using guided regularized random forest and feature selection, our method achieved high performance and outperformed a traditional enrichment-based method in selecting candidate regulatory genes. Our method is particularly efficient in selecting a few candidate genes to explain observed expression pattern. In particular, among 531 candidate TFs, our method achieves an auROC of 0.961 with only 10 motifs. Finally, we found two novel subpopulations of monocyte cells in response to SD-LPS and we confirmed our analysis using independent flow cytometry experiments. Our results suggest that our new machine learning method can select candidate regulatory genes as potential targets for developing new therapeutics against low grade inflammation.

Indexed as

Machine LearningAnimalsGene Regulatory NetworksLipopolysaccharidesMaleMiceMice, Inbred C57BLMonocytesPhenylbutyratesQuality ControlRNA-SeqSingle-Cell Analysis4-phenylbutyric acidLipopolysaccharidesPhenylbutyratesinflammationmachine learningmonocyteregulatory motifssingle cell analysis

Identifiers

PMID33708217
PMCPMC7940189
OpenAlexW3131527477

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.