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量子通用交换语言在精准医学和药物先导发现中的扩展。使用线粒体基因组的初步实例研究。

Extension of the Quantum Universal Exchange Language to precision medicine and drug lead discovery. Preliminary example studies using the mitochondrial genome.

作者信息

Robson Barry

机构信息

Ingine Inc., Delaware, USA; The Dirac Foundation, OxfordShire, UK.

出版信息

Comput Biol Med. 2020 Feb;117:103621. doi: 10.1016/j.compbiomed.2020.103621. Epub 2020 Jan 20.

Abstract

The Quantum Universal Exchange Language (Q-UEL) based on Dirac notation and algebra from quantum mechanics, along with its associated data mining and Hyperbolic Dirac Net (HDN) for probabilistic inference, has proven to be a useful architectural principle for knowledge management, analysis and prediction systems in medicine. It has been described in several papers; here is described its extension to clinical genomics and precision medicine. Two use cases are studied: (a) bioinformatics in clinical decision support especially for risk for type 2 diabetes using mitochondrial patient DNA sequences, and (b) bioinformatics and computational biology (conformational) research examples related to drug discovery involving the recently discovered class of mitochondrial derived peptides (MDPs). MDPs were surprising when first discovered as coded in small open reading frames (sORFs), and are emerging as having a fundamental role in metabolic control, longevity and disease. This project originally represented a language specification study relating to what information related to genomics is essential or useful to carry, and what processing will be needed. However, novel aspects introduced or discovered include the HDN-like neural nets and their use, along with more established methods, for prediction of type 2 diabetes, and in particular for proposals for over 80 natural MDPs most of which that have not previously been described at the time of the study, as potential drug lead targets. Also, use of many medical records with simulated joining of mtDNA as performance tests led to some insightful observations regarding the behavior of HDN predictions where independent factors are involved.

摘要

基于量子力学中狄拉克符号和代数的量子通用交换语言(Q-UEL)及其相关的数据挖掘和用于概率推理的双曲狄拉克网络(HDN),已被证明是医学知识管理、分析和预测系统的一种有用的架构原则。已有多篇论文对其进行了描述;本文介绍了其在临床基因组学和精准医学方面的扩展。研究了两个用例:(a)临床决策支持中的生物信息学,特别是利用线粒体患者DNA序列预测2型糖尿病风险;(b)与药物发现相关的生物信息学和计算生物学(构象)研究实例,涉及最近发现的线粒体衍生肽(MDP)类别。MDP最初在小开放阅读框(sORF)中被编码时令人惊讶,并且正逐渐显现出在代谢控制、长寿和疾病中具有重要作用。该项目最初是一项关于携带哪些与基因组学相关的信息至关重要或有用以及需要进行何种处理的语言规范研究。然而,引入或发现的新方面包括类似HDN的神经网络及其用途,以及与更成熟的方法一起用于预测2型糖尿病,特别是对于80多种天然MDP的提议,其中大多数在研究时尚未被描述,作为潜在的药物先导靶点。此外,使用许多带有模拟线粒体DNA连接的医疗记录作为性能测试,得出了一些关于涉及独立因素时HDN预测行为的深刻见解。

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