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Toward predictable universal genetic circuit design

Quantitative Biology 2024年第2期12卷 225-229页

作者： Yuanli Gao Baojun Wang College of Chemical and Biological Engineering Zhejiang UniversityHangzhouChina ZJU-Hangzhou Global Scientific and Technological Innovation Center Zhejiang UniversityHangzhouChina School of Biological Sciences University of EdinburghEdinburghUK

In thepast 2decades,synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors,such as Boolean logic gates,signal filters,oscillators,state machines,perceptrons,and genetic controllers[1,2].Following a bottom-up strategy,the genetic circuits are designed by assembling a set of well-characterized biological components,or genetic parts[3],and optimized through the iterative design-Build-Test-Learn(DBTL)cycles.

关键词： circuit predictability genetic circuit design host independent part characterization portability

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End-to-end computational approach to the design of RNA biosensors for detecting miRNA biomarkers of cervical cancer

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Synthetic and Systems Biotechnology 2022年第2期7卷 802-814页

作者： Priyannth Ramasami S.Baabu Shivaramakrishna Srinivasan Swetha Nagarajan Sangeetha Muthamilselvan Thamarai Selvi Raghavv R.Suresh Ashok Palaniappan Department of Bioinformatics School of Chemical and BiotechnologySASTRA Deemed UniversityThanjavurTamil Nadu 613401India Department of Bioengineering School of Chemical and BiotechnologySASTRA Deemed UniversityThanjavurTamil Nadu613401India School of Advanced Materials Science and Engineering Sungkyunkwan University(SKKU)Suwon16419Republic of Korea Life Sciences Division TCS ResearchTata Consultancy ServicesChennaiTamil Nadu600042India

Cervical cancer is a global public health subject as it affects women in the reproductive ages,and accounts for the second largest burden among cancer patients worldwide with an unforgiving 50%mortality *** scant awareness and limited access to effective diagnosis have led to this enormous disease burden,calling for point-of-care,minimally invasive diagnosis ***,an end-to-end quantitative unified pipeline for diagnosis has been developed,beginning with identification of optimal biomarkers,concurrent design of toehold switch sensors,and finally simulation of the designed diagnostic circuits to assess *** miRNA expression data in the public domain,we identified miR-21-5p and miR-20a-5p as blood-based miRNA biomarkers specific to early-stage cervical cancer employing a multi-tier algorithmic *** riboregulators called toehold switches specific to the biomarker panel were then *** predict the dynamic range of toehold switches for use in genetic circuits as biosensors,we used a generic grammar of these switches,and built a neural network model of dynamic range using thermodynamic features derived from mRNA secondary structure and ***-generation toehold switches were used to overcome the design challenges associated with miRNA *** resultant model yielded an adj.R^(2)~0.71,outperforming earlier models of toehold-switch dynamic *** kinetics modelling was performed to predict the sensitivity of the second-generation toehold switches to the miRNA *** showed a linear response between 10 nM and 100 nM before *** study demonstrates an end-to-end computational workflow for the efficient design of genetic circuits geared towards the effective detection of unique genomic/nucleic-acid *** approach has the potential to replace iterative experimental trial and error,and focus time,money,and *** software including the toehold grammar parser,neu

关键词： Cervical cancer biosensor miRNA biomarker Synthetic toehold switches genetic circuit design Reaction network modelling Toehold efficacy modelling Toehold switch grammar Machine learning

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