Evidence map›Paper›PMID 34267310›Full record

ArticleCommunications biology2021

Quantitative characterization of recombinase-based digitizer circuits enables predictable amplification of biological signals.

Katherine A Kiwimagi, Justin H Letendre, Benjamin H Weinberg, Junmin Wang, Mingzhe Chen, Leandro Watanabe, Chris J Myers, Jacob Beal, Wilson W Wong, Ron Weiss

Abstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Temperature-Dependent Recombinase-Based Genetic Circuits.International journal of molecular sciences · 2025
    Article
  2. Article
  3. Article
  4. Article
  5. Functional Synthetic Biology.Synthetic biology (Oxford, England) · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. 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

10 authors.

Katherine A Kiwimagi *Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Justin H Letendre *Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.
Benjamin H WeinbergDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.ORCID 0000-0003-2604-2260
Junmin WangThe Bioinformatics Graduate Program, Boston University, Boston, MA, USA.ORCID 0000-0003-3413-2004
Mingzhe ChenBiological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Leandro WatanabeDepartment of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT, USA.
Chris J MyersDepartment of Electrical and Computer Engineering, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-8762-8444
Jacob BealRaytheon BBN Technologies, Cambridge, MA, USA. jake.beal@raytheon.com.
Wilson W WongDepartment of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA. wilwong@bu.edu.ORCID 0000-0001-8394-889X
Ron WeissBiological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. rweiss@mit.edu.ORCID 0000-0003-0396-2443

Funding

Synthetically Reengineered T cells as the Next Generation of Smart Cancer TherapyDP2CA186574 · NCI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI WONG, WILSON · 2013 to 2013
$2.5M
Advanced recombinase-based gene expression technology in mammalian cellsR01GM129011 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI WONG, WILSON · 2019 to 2022
$1.5M
Advanced Recombinase Technology for Tissue Engineering ApplicationsF31HL149334 · NHLBI · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI LETENDRE, JUSTIN HENRY · 2019 to 2021
$88k
NCI NIH HHS DP2 CA186574NHLBI NIH HHS F31 HL149334NIGMS NIH HHS R01 GM129011
6 · The paper itself

Abstract

Many synthetic gene circuits are restricted to single-use applications or require iterative refinement for incorporation into complex systems. One example is the recombinase-based digitizer circuit, which has been used to improve weak or leaky biological signals. Here we present a workflow to quantitatively define digitizer performance and predict responses to different input signals. Using a combination of signal-to-noise ratio (SNR), area under a receiver operating characteristic curve (AUC), and fold change (FC), we evaluate three small-molecule inducible digitizer designs demonstrating FC up to 508x and SNR up to 3.77 dB. To study their behavior further and improve modularity, we develop a mixed phenotypic/mechanistic model capable of predicting digitizer configurations that amplify a synNotch cell-to-cell communication signal (Δ SNR up to 2.8 dB). We hope the metrics and modeling approaches here will facilitate incorporation of these digitizers into other systems while providing an improved workflow for gene circuit characterization.

Indexed as

Signal TransductionGenetic EngineeringRecombinasesROC CurveSynthetic BiologyRecombinases

Identifiers

PMID34267310
PMCPMC8282836

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.