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1.
ACS Synth Biol ; 13(5): 1424-1433, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38684225

ABSTRACT

The ability to control cellular processes using optogenetics is inducer-limited, with most optogenetic systems responding to blue light. To address this limitation, we leverage an integrated framework combining Lustro, a powerful high-throughput optogenetics platform, and machine learning tools to enable multiplexed control over blue light-sensitive optogenetic systems. Specifically, we identify light induction conditions for sequential activation as well as preferential activation and switching between pairs of light-sensitive split transcription factors in the budding yeast, Saccharomyces cerevisiae. We use the high-throughput data generated from Lustro to build a Bayesian optimization framework that incorporates data-driven learning, uncertainty quantification, and experimental design to enable the prediction of system behavior and the identification of optimal conditions for multiplexed control. This work lays the foundation for designing more advanced synthetic biological circuits incorporating optogenetics, where multiple circuit components can be controlled using designer light induction programs, with broad implications for biotechnology and bioengineering.


Subject(s)
Bayes Theorem , Optogenetics , Saccharomyces cerevisiae , Optogenetics/methods , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Synthetic Biology/methods , Light , Transcription Factors/metabolism , Transcription Factors/genetics , Machine Learning , High-Throughput Screening Assays/methods
2.
bioRxiv ; 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38187522

ABSTRACT

The ability to control cellular processes using optogenetics is inducer-limited, with most optogenetic systems responding to blue light. To address this limitation we leverage an integrated framework combining Lustro, a powerful high-throughput optogenetics platform, and machine learning tools to enable multiplexed control over blue light-sensitive optogenetic systems. Specifically, we identify light induction conditions for sequential activation as well as preferential activation and switching between pairs of light-sensitive spit transcription factors in the budding yeast, Saccharomyces cerevisiae . We use the high-throughput data generated from Lustro to build a Bayesian optimization framework that incorporates data-driven learning, uncertainty quantification, and experimental design to enable the prediction of system behavior and the identification of optimal conditions for multiplexed control. This work lays the foundation for designing more advanced synthetic biological circuits incorporating optogenetics, where multiple circuit components can be controlled using designer light induction programs, with broad implications for biotechnology and bioengineering.

3.
Comput Chem Eng ; 179: 1-12, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38264312

ABSTRACT

Anthropogenic pollution of hydrological systems affects diverse communities and ecosystems around the world. Data analytics and modeling tools play a key role in fighting this challenge, as they can help identify key sources as well as trace transport and quantify impact within complex hydrological systems. Several tools exist for simulating and tracing pollutant transport throughout surface waters using detailed physical models; these tools are powerful, but can be computationally intensive, require significant amounts of data to be developed, and require expert knowledge for their use (ultimately limiting application scope). In this work, we present a graph modeling framework - which we call HydroGraphs - for understanding pollutant transport and fate across waterbodies, rivers, and watersheds. This framework uses a simplified representation of hydrological systems that can be constructed based purely on open-source data (National Hydrography Dataset and Watershed Boundary Dataset). The graph representation provides a flexible intuitive approach for capturing connectivity and for identifying upstream pollutant sources and for tracing downstream impacts within small and large hydrological systems. Moreover, the graph representation can facilitate the use of advanced algorithms and tools of graph theory, topology, optimization, and machine learning to aid data analytics and decision-making. We demonstrate the capabilities of our framework by using case studies in the State of Wisconsin; here, we aim to identify upstream nutrient pollutant sources that arise from agricultural practices and trace downstream impacts to waterbodies, rivers, and streams. Our tool ultimately seeks to help stakeholders design effective pollution prevention/mitigation practices and evaluate how surface waters respond to such practices.

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