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1.
Proc Mach Learn Res ; 126: 871-894, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35072085

RESUMO

Managing a chronic disease like Type 1 diabetes (T1D) is both challenging and time consuming, but new technologies that allow continuous measurement of glucose and delivery of insulin have led to significant improvements. The development of an artificial pancreas (AP), which algorithmically determines insulin dosing and delivers insulin in a fully automated way, may transform T1D care but it is not yet widely available. Patient-led alternatives, like the Open Artificial Pancreas (OpenAPS), are being used by hundreds of individuals and have also led to a dramatic increase in the availability of patient generated health data (PGHD). All APs require an accurate forecast of blood glucose (BG). While there have been efforts to develop better forecasts and apply new ML techniques like deep learning to this problem, methods are often tested on small controlled datasets that do not indicate how they may perform in reality - and the most advanced methods have not always outperformed the simplest. We introduce a rigorous comparison of BG forecasting using both a small controlled research dataset and large heterogeneous PGHD. Our comparison advances the state of the art in BG forecasting by providing insight into how methods may fare when moving beyond small controlled studies to real-world use.

2.
Sci Rep ; 8(1): 3554, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29476134

RESUMO

Boolean modelling of biological networks is a well-established technique for abstracting dynamical biomolecular regulation in cells. Specifically, decoding linkages between salient regulatory network states and corresponding cell fate outcomes can help uncover pathological foundations of diseases such as cancer. Attractor landscape analysis is one such methodology which converts complex network behavior into a landscape of network states wherein each state is represented by propensity of its occurrence. Towards undertaking attractor landscape analysis of Boolean networks, we propose an Attractor Landscape Analysis Toolbox (ATLANTIS) for cell fate discovery, from biomolecular networks, and reprogramming upon network perturbation. ATLANTIS can be employed to perform both deterministic and probabilistic analyses. It has been validated by successfully reconstructing attractor landscapes from several published case studies followed by reprogramming of cell fates upon therapeutic treatment of network. Additionally, the biomolecular network of HCT-116 colorectal cancer cell line has been screened for therapeutic evaluation of drug-targets. Our results show agreement between therapeutic efficacies reported by ATLANTIS and the published literature. These case studies sufficiently highlight the in silico cell fate prediction and therapeutic screening potential of the toolbox. Lastly, ATLANTIS can also help guide single or combinatorial therapy responses towards reprogramming biomolecular networks to recover cell fates.


Assuntos
Linhagem da Célula/genética , Reprogramação Celular/genética , Simulação por Computador , Software , Diferenciação Celular/genética , Redes Reguladoras de Genes/genética , Células HCT116 , Humanos , Modelos Genéticos , Transdução de Sinais/genética
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