Dataset Information

Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

ABSTRACT: A major pharmacological assumption is that lowering disease-promoting protein levels is generally beneficial. For example, inhibiting metastasis activator BACH1 is proposed to decrease cancer metastases. Testing such assumptions requires approaches to measure disease phenotypes while precisely adjusting disease-promoting protein levels. Here we developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic safe harbor locus. Unexpectedly, engineered MDA-MB-231 metastatic human breast cancer cells become more, then less and then more invasive as we tune BACH1 levels up, irrespective of the native BACH1. BACH1 expression shifts in invading cells, and expression of BACH1's transcriptional targets confirm BACH1's nonmonotone phenotypic and regulatory effects. Thus, chemical inhibition of BACH1 could have unwanted effects on invasion. Additionally, BACH1's expression variability aids invasion at high BACH1 expression. Overall, precisely engineered, noise-aware protein-level control is necessary and important to unravel disease effects of genes to improve clinical drug efficacy.

SUBMITTER: Wan Y

PROVIDER: S-EPMC10299915 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

Wan Yiming Y Cohen Joseph J Szenk Mariola M Farquhar Kevin S KS Coraci Damiano D Krzysztoń Rafał R Azukas Joshua J Van Nest Nicholas N Smashnov Alex A Chern Yi-Jye YJ De Martino Daniela D Nguyen Long Chi LC Bien Harold H Bravo-Cordero Jose Javier JJ Chan Chia-Hsin CH Rosner Marsha Rich MR Balázsi Gábor G

Nature chemical biology 20230525 7

A major pharmacological assumption is that lowering disease-promoting protein levels is generally beneficial. For example, inhibiting metastasis activator BACH1 is proposed to decrease cancer metastases. Testing such assumptions requires approaches to measure disease phenotypes while precisely adjusting disease-promoting protein levels. Here we developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic safe harbor locus. ...[more]

PMID: 37231268

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Project description:BackgroundLow-dose X-ray images have become increasingly popular in the last decades, due to the need to guarantee the lowest reasonable patient's exposure. Dose reduction causes a substantial increase of quantum noise, which needs to be suitably suppressed. In particular, real-time denoising is required to support common interventional fluoroscopy procedures. The knowledge of noise statistics provides precious information that helps to improve denoising performances, thus making noise estimation a crucial task for effective denoising strategies. Noise statistics depend on different factors, but are mainly influenced by the X-ray tube settings, which may vary even within the same procedure. This complicates real-time denoising, because noise estimation should be repeated after any changes in tube settings, which would be hardly feasible in practice. This work investigates the feasibility of an a priori characterization of noise for a single fluoroscopic device, which would obviate the need for inferring noise statics prior to each new images acquisition. The noise estimation algorithm used in this study was tested in silico to assess its accuracy and reliability. Then, real sequences were acquired by imaging two different X-ray phantoms via a commercial fluoroscopic device at various X-ray tube settings. Finally, noise estimation was performed to assess the matching of noise statistics inferred from two different sequences, acquired independently in the same operating conditions.ResultsThe noise estimation algorithm proved capable of retrieving noise statistics, regardless of the particular imaged scene, also achieving good results even by using only 10 frames (mean percentage error lower than 2%). The tests performed on the real fluoroscopic sequences confirmed that the estimated noise statistics are independent of the particular informational content of the scene from which they have been inferred, as they turned out to be consistent in sequences of the two different phantoms acquired independently with the same X-ray tube settings.ConclusionsThe encouraging results suggest that an a priori characterization of noise for a single fluoroscopic device is feasible and could improve the actual implementation of real-time denoising strategies that take advantage of noise statistics to improve the trade-off between noise reduction and details preservation.

Dataset Information

Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

Publications

Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.

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