Evidence map›Paper›PMID 36716175›Full record

ArticleJournal of the American Chemical Society2023

Resolving Molecular Heterogeneity with Single-Molecule Centrifugation.

Yi Luo, Jeffrey Chang, Darren Yang, J Shepard Bryan, Molly MacIsaac, Steve Pressé, Wesley P Wong

Open access · hybridAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 18 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Yi LuoProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, United States.
Jeffrey ChangDepartment of Physics, Harvard University, Cambridge, Massachusetts 02138, United States.
Darren YangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, United States.
J Shepard BryanDepartment of Physics, Arizona State University, Tempe, Arizona 85287, United States.
Molly MacIsaacProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, United States.
Steve PresséDepartment of Physics, Arizona State University, Tempe, Arizona 85287, United States.ORCID 0000-0002-5408-0718
Wesley P WongProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, United States.ORCID 0000-0001-7398-546X
Boston Children's Hospital · USArizona State University · USHarvard University · US

Funding

Mechanical forces in nanoscale biology: From hemostasis to single-molecule centrifugationR35GM119537 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI Wesley Philip Wong · 2016 to 2026
$5.2M
A Bayesian nonparametric approach to superresolved tracking of multiple molecules inside living cellsR01GM130745 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI PRESSE, STEVE · 2019 to 2023
$1.5M
Theoretical Models of Single Molecule Dynamics from Minimal Photon NumbersR01GM134426 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI PRESSE, STEVE · 2019 to 2022
$1.2M
6 · The paper itself

Abstract

For many classes of biomolecules, population-level heterogeneity is an essential aspect of biological function─from antibodies produced by the immune system to post-translationally modified proteins that regulate cellular processes. However, heterogeneity is difficult to fully characterize for multiple reasons: (i) single-molecule approaches are needed to avoid information lost by ensemble-level averaging, (ii) sufficient statistics must be gathered on both a per-molecule and per-population level, and (iii) a suitable analysis framework is required to make sense of a potentially limited number of intrinsically noisy measurements. Here, we introduce an approach that overcomes these difficulties by combining three techniques: a DNA nanoswitch construct to repeatedly interrogate the same molecule, a benchtop centrifuge force microscope (CFM) to obtain thousands of statistics in a highly parallel manner, and a Bayesian nonparametric (BNP) inference method to resolve separate subpopulations with distinct kinetics. We apply this approach to characterize commercially available antibodies and find that polyclonal antibody from rabbit serum is well-modeled by a mixture of three subpopulations. Our results show how combining a spatially and temporally multiplexed nanoswitch-CFM assay with BNP analysis can help resolve complex biomolecular interactions in heterogeneous samples.

Indexed as

AntibodiesNanotechnologyAnimalsBayes TheoremCentrifugationHumansKineticsMicroscopy, Atomic ForceRabbitsAntibodies

Identifiers

PMID36716175
PMCPMC9936575
OpenAlexW4318486460

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.