Evidence map›Paper›PMID 33424024›Full record

ArticleNature protocols2021

A robust unsupervised machine-learning method to quantify the morphological heterogeneity of cells and nuclei.

Jude M Phillip, Kyu-Sang Han, Wei-Chiang Chen, Denis Wirtz, Pei-Hsun Wu

Abstract read
In one paragraph

Article in Nature protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing 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

73 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Behavioral and Functional Profiling ofbioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Target identification and assessment in the era of AI.Nature reviews. Drug discovery · 2026
    Review
  8. Article
  9. Review
  10. Cell-nanoplastics association impacts cell proliferation and motility.bioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Leveraging AI for cell biology discovery.Biochemical Society transactions · 2026
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Curved Magnetic Hydrogels for Understanding Cancer Initiation.ACS applied materials & interfaces · 2025
    Article
  20. Article

13 more citing papers are in PubMed but not listed here.

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

5 authors.

Jude M Phillip *Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins Institute for Nanobiotechnology (INBT), Johns Hopkins University, Baltimore, MD, USA.
Kyu-Sang Han *Department of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins Institute for Nanobiotechnology (INBT), Johns Hopkins University, Baltimore, MD, USA.
Wei-Chiang ChenDepartment of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins Institute for Nanobiotechnology (INBT), Johns Hopkins University, Baltimore, MD, USA.
Denis WirtzDepartment of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins Institute for Nanobiotechnology (INBT), Johns Hopkins University, Baltimore, MD, USA. wirtz@jhu.edu.ORCID http://orcid.org/0000-0001-6147-3045
Pei-Hsun WuDepartment of Chemical and Biomolecular Engineering, Johns Hopkins Physical Sciences Oncology Center, Johns Hopkins Institute for Nanobiotechnology (INBT), Johns Hopkins University, Baltimore, MD, USA. pwu@jhu.edu.ORCID http://orcid.org/0000-0002-7371-2960

Funding

Technological Assessment and Solutions Core - RC4P30AG021334 · NIA · JOHNS HOPKINS UNIVERSITY · PI Jeremy D Walston · 2003 to 2026
$33.2M
TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEARSON, PETER C · 2009 to 2013
$13.7M
The Role of Physical Cues in Collective Cell InvasionU54CA210173 · NCI · JOHNS HOPKINS UNIVERSITY · PI PIENTA, KENNETH J., WIRTZ, DENIS · 2016 to 2020
$9.9M
Single-cell phenotyping for therapeutic stratification in pancreatic cancerR01CA174388 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2012 to 2016
$3.8M
Validation of Nuclear Morphology as a Biomarker of Aging and Aging-Related PhenotypesU01AG060903 · NIA · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2018 to 2022
$3.1M
NCI NIH HHS R01 CA174388NCI NIH HHS U54 CA143868NCI NIH HHS U54 CA210173NIA NIH HHS P30 AG021334NIA NIH HHS U01 AG060903U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA174388U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA143868U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG060903
6 · The paper itself

Abstract

Cell morphology encodes essential information on many underlying biological processes. It is commonly used by clinicians and researchers in the study, diagnosis, prognosis, and treatment of human diseases. Quantification of cell morphology has seen tremendous advances in recent years. However, effectively defining morphological shapes and evaluating the extent of morphological heterogeneity within cell populations remain challenging. Here we present a protocol and software for the analysis of cell and nuclear morphology from fluorescence or bright-field images using the VAMPIRE algorithm ( https://github.com/kukionfr/VAMPIRE_open ). This algorithm enables the profiling and classification of cells into shape modes based on equidistant points along cell and nuclear contours. Examining the distributions of cell morphologies across automatically identified shape modes provides an effective visualization scheme that relates cell shapes to cellular subtypes based on endogenous and exogenous cellular conditions. In addition, these shape mode distributions offer a direct and quantitative way to measure the extent of morphological heterogeneity within cell populations. This protocol is highly automated and fast, with the ability to quantify the morphologies from 2D projections of cells seeded both on 2D substrates or embedded within 3D microenvironments, such as hydrogels and tissues. The complete analysis pipeline can be completed within 60 minutes for a dataset of ~20,000 cells/2,400 images.

Indexed as

AlgorithmsCell NucleusCell ShapeHumansImaging, Three-DimensionalMicroscopy, ConfocalSoftwareUnsupervised Machine Learning

Identifiers

PMID33424024
PMCPMC8167883

What OpenQuestion holds

Textmetadata
LicenceTDM
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.