Evidence map›Paper›PMID 34533995›Full record

ArticleScience advances2021

Massively parallel quantification of phenotypic heterogeneity in single-cell drug responses.

Benjamin B Yellen, Jon S Zawistowski, Eric A Czech, Caleb I Sanford, Elliott D SoRelle, Micah A Luftig, Zachary G Forbes, Kris C Wood, Jeff Hammerbacher

Abstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. 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

9 authors.

Benjamin B YellenDepartment of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0002-8669-6752
Jon S ZawistowskiCelldom Inc., San Carlos, CA 94070, USA.ORCID 0000-0001-8493-9813
Eric A CzechDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0002-4254-4255
Caleb I SanfordDepartment of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.ORCID 0000-0001-5027-4198
Elliott D SoRelleDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University, Durham, NC 27708, USA.ORCID 0000-0002-3362-1028
Micah A LuftigDepartment of Molecular Genetics and Microbiology, Center for Virology, Duke University, Durham, NC 27708, USA.ORCID 0000-0002-2964-1907
Zachary G ForbesCelldom Inc., San Carlos, CA 94070, USA.
Kris C WoodCelldom Inc., San Carlos, CA 94070, USA.ORCID 0000-0002-5887-2253
Jeff HammerbacherDepartment of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.ORCID 0000-0001-6596-8563

Funding

Viral Oncology Training GrantT32CA009111 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH A. · 1985 to 2023
$8.9M
Host pathways regulating Epstein-Barr virus-mediated B cell growth transformationR01CA140337 · NCI · DUKE UNIVERSITY · PI LUFTIG, MICAH ALAN · 2011 to 2025
$5.9M
High-throughput screening of arrayed single cells for automated analysis of phenotypic heterogeneityR44GM122149 · NIGMS · CELLDOM, INC. · PI FORBES, ZACHARY GRAHAM · 2018 to 2019
$1.5M
Image-Seq: A high-density microfluidic trap array for single cell transcriptome analysis coupled with image based phenotypingR21GM131279 · NIGMS · DUKE UNIVERSITY · PI TATA, PURUSHOTHAMA RAO · 2018 to 2019
$432k
Single cell functional dissection of tumor microenviornment-driven drug resistanceR21CA220082 · NCI · DUKE UNIVERSITY · PI WOOD, KRIS C. · 2018 to 2019
$359k
High-throughput screening of arrayed single cells for automated analysis of phenotypic heterogeneityR43GM122149 · NIGMS · CELLDOM, INC. · PI FORBES, ZACHARY GRAHAM · 2017 to 2017
$225k
NCI NIH HHS R01 CA140337NCI NIH HHS R21 CA220082NCI NIH HHS T32 CA009111NIGMS NIH HHS R21 GM131279NIGMS NIH HHS R43 GM122149NIGMS NIH HHS R44 GM122149
6 · The paper itself

Abstract

Single-cell analysis tools have made substantial advances in characterizing genomic heterogeneity; however, tools for measuring phenotypic heterogeneity have lagged due to the increased difficulty of handling live biology. Here, we report a single-cell phenotyping tool capable of measuring image-based clonal properties at scales approaching 100,000 clones per experiment. These advances are achieved by exploiting a previously unidentified flow regime in ladder microfluidic networks that, under appropriate conditions, yield a mathematically perfect cell trap. Machine learning and computer vision tools are used to control the imaging hardware and analyze the cellular phenotypic parameters within these images. Using this platform, we quantified the responses of tens of thousands of single cell–derived acute myeloid leukemia (AML) clones to targeted therapy, identifying rare resistance and morphological phenotypes at frequencies down to 0.05%. This approach can be extended to higher-level cellular architectures such as cell pairs and organoids and on-chip live-cell fluorescence assays.

Indexed as

Leukemia, Myeloid, AcuteClone CellsHumansMicrofluidicsPhenotypeSingle-Cell Analysis

Identifiers

PMID34533995
PMCPMC8448449

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.