Evidence map›Paper›PMID 28682059›Full record

ArticleACS combinatorial science2017

Poisson Statistics of Combinatorial Library Sampling Predict False Discovery Rates of Screening.

Andrew B MacConnell, Brian M Paegel

Abstract read
In one paragraph

Article in ACS combinatorial science, 2017. 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
–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

16 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Translating the Genome into Drugs.Accounts of chemical research · 2023
    Article
  9. Article
  10. DNA-encoded library versus RNA-encoded library selection enables design of an oncogenic noncoding RNA inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  11. Engineering Proteins Containing Noncanonical Amino Acids on the Yeast Surface.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  12. Article
  13. Review
  14. Article
  15. Off-DNA DNA-Encoded Library Affinity Screening.ACS combinatorial science · 2020
    Article
  16. Activity-Based DNA-Encoded Library Screening.ACS combinatorial science · 2019
    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

2 authors.

Andrew B MacConnellDepartment of Chemistry and †Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
Brian M PaegelDepartment of Chemistry and †Doctoral Program in Chemical and Biological Sciences, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.ORCID 0000-0002-6531-6693

Funding

High-Throughput Droplet-Scale Functional Screening of DNA-Encoded Combinatorial LibrariesR01GM120491 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PAEGEL, BRIAN M · 2017 to 2020
$1.4M
NIGMS NIH HHS R01 GM120491
6 · The paper itself

Abstract

Microfluidic droplet-based screening of DNA-encoded one-bead-one-compound combinatorial libraries is a miniaturized, potentially widely distributable approach to small molecule discovery. In these screens, a microfluidic circuit distributes library beads into droplets of activity assay reagent, photochemically cleaves the compound from the bead, then incubates and sorts the droplets based on assay result for subsequent DNA sequencing-based hit compound structure elucidation. Pilot experimental studies revealed that Poisson statistics describe nearly all aspects of such screens, prompting the development of simulations to understand system behavior. Monte Carlo screening simulation data showed that increasing mean library sampling (ε), mean droplet occupancy, or library hit rate all increase the false discovery rate (FDR). Compounds identified as hits on k > 1 beads (the replicate k class) were much more likely to be authentic hits than singletons (k = 1), in agreement with previous findings. Here, we explain this observation by deriving an equation for authenticity, which reduces to the product of a library sampling bias term (exponential in k) and a sampling saturation term (exponential in ε) setting a threshold that the k-dependent bias must overcome. The equation thus quantitatively describes why each hit structure's FDR is based on its k class, and further predicts the feasibility of intentionally populating droplets with multiple library beads, assaying the micromixtures for function, and identifying the active members by statistical deconvolution.

Indexed as

Computer SimulationCombinatorial Chemistry TechniquesDNAHigh-Throughput Screening AssaysMicrofluidic Analytical TechniquesMicrospheresMonte Carlo MethodSmall Molecule LibrariesDNASmall Molecule Librariescombinatorial librariesfalse discovery ratesMonte Carlo screeningone-bead-one-compoundPoisson statistics

Identifiers

PMID28682059
PMCPMC5558193

What OpenQuestion holds

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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.