Evidence map›Paper›PMID 27790993›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Controlling uncertainty in aptamer selection.

Fabian Spill, Zohar B Weinstein, Atena Irani Shemirani, Nga Ho, Darash Desai, Muhammad H Zaman

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
  5. In vitro selection of aptamers and their applications.Nature reviews. Methods primers · 2023
    Article
  6. Article
  7. Article
  8. A system for multiplexed selection of aptamers with exquisite specificity without counterselection.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Aptamer Bioinformatics.International journal of molecular sciences · 2017
    Review
  17. Emerging cancer-specific therapeutic aptamers.Current opinion in oncology · 2017
    Review
  18. 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

6 authors.

Fabian SpillDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biomedical Engineering, Boston University, Boston MA 02215.
Zohar B WeinsteinDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118.
Atena Irani ShemiraniDepartment of Biomedical Engineering, Boston University, Boston MA 02215.
Nga HoDepartment of Biomedical Engineering, Boston University, Boston MA 02215.
Darash DesaiDepartment of Biomedical Engineering, Boston University, Boston MA 02215; ddesai@bu.edu zaman@bu.edu.
Muhammad H ZamanDepartment of Biomedical Engineering, Boston University, Boston MA 02215; Howard Hughes Medical Institute, Boston University, Boston, MA 02215 ddesai@bu.edu zaman@bu.edu.

Funding

TRAINING IN BIOMOLECULAR PHARMACOLOGYT32GM008541 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, DAVID H · 1997 to 2022
$5.2M
Modeling bi-directional signaling and cytoskeletal dynamics in 3D cell migrationsU01CA177799 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI GERTLER, FRANK B, KAMM, ROGER D · 2013 to 2017
$3.0M
NCI NIH HHS U01 CA177799NIGMS NIH HHS T32 GM008541
6 · The paper itself

Abstract

The search for high-affinity aptamers for targets such as proteins, small molecules, or cancer cells remains a formidable endeavor. Systematic Evolution of Ligands by EXponential Enrichment (SELEX) offers an iterative process to discover these aptamers through evolutionary selection of high-affinity candidates from a highly diverse random pool. This randomness dictates an unknown population distribution of fitness parameters, encoded by the binding affinities, toward SELEX targets. Adding to this uncertainty, repeating SELEX under identical conditions may lead to variable outcomes. These uncertainties pose a challenge when tuning selection pressures to isolate high-affinity ligands. Here, we present a stochastic hybrid model that describes the evolutionary selection of aptamers to explore the impact of these unknowns. To our surprise, we find that even single copies of high-affinity ligands in a pool of billions can strongly influence population dynamics, yet their survival is highly dependent on chance. We perform Monte Carlo simulations to explore the impact of environmental parameters, such as the target concentration, on selection efficiency in SELEX and identify strategies to control these uncertainties to ultimately improve the outcome and speed of this time- and resource-intensive process.

Indexed as

Aptamers, NucleotideBinding, CompetitiveBinding SitesHumansKineticsLigandsMonte Carlo MethodNucleic AcidsProteinsSELEX Aptamer TechniqueSmall Molecule LibrariesStochastic ProcessesUncertaintyAptamers, NucleotideLigandsNucleic AcidsProteinsSmall Molecule Librariesaptamerevolutionary dynamicshybrid modelSELEXstochastic process

Identifiers

PMID27790993
PMCPMC5087011

What OpenQuestion holds

Textmetadata
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.