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Integrative technologies in precision medicine

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Published: 25 Mar 2019
By Zahra Rattray, Nicholas Rattray

From the latter end of the twentieth century we have seen an unprecedented bench-to-clinic transition of novel medicines in the clinical management of a diversity of pathologies. With such a rapid expansion in the pharmacological toolbox, evidence of population heterogeneity in drug safety and efficacy has come under the spotlight. Long gone is the concept of drugs as magic bullets and diseases as a single clean target, but the perspective that numerous diseases are phenotypically heterogeneous across the patient population. This paradigm shift has been a main driver behind the era of ‘precision medicine’ in which integrated and individualised approaches to the pharmacotherapeutic management of disease are being pursued.

The concept of precision medicine, in which treatment decisions are based on holistic consideration of an individual’s genetic makeup, lifestyle and environmental exposures is not new but has taken on a different perspective in modern medicine. In the quest for achieving safe and cost-effective healthcare, government-led global initiatives have formed to deliver on the precision medicine agenda. The Precision Medicine Initiative (PMI), ‘All of Us’, formed by the National Institutes of Health (NIH, USA), has seen collaborative efforts between university, government, industry and non-profit sectors on an unprecedented scale. The goal central to such initiatives is to provide insights that will inform the design and development of new medicines, repurpose currently-available drugs, predict response to drug treatment, and design new personalised drug combinations. Since the establishment of the PMI, several similar Asian and European initiatives have emerged to address disparities in the pharmacological management of diseases within their populations.

Beyond precision medicine initiatives, biobanks have emerged as an invaluable resource in progressing modern day precision medicine efforts -  The ‘UK Biobank’, an open-access resource, has been a large success in providing researchers with access to genetic, phenotypic and clinical data from a cohort of 500,000 UK patients. A key to the success of biobanks and precision medicine initiatives has been the digitalisation and centralisation of patient health records that has streamlined patient recruitment, and enabled tracking of participant disease course through accessing treatment outcomes and prognoses over time. Following the many successes of the UK Biobank, the 100,000 genomes scheme emerged, sequencing the genome of 1 million NHS patients and UK Biobank participants. Since the UK Biobank became available to researchers in 2012, there have been in excess of 8,000 approved researcher registrations from across the globe and 800 registered projects, the culmination of which has been over 500 publications.

Central to the successful delivery of precision medicine initiatives are global interdisciplinary technological advancements that integrate and standardise analytical pipelines, alongside the management of big data produced. Novel technological advancements since the human genome project have given rise to the era of systems biology. The application of high-throughput analytical technologies has enabled scientists and clinicians to closely interrogate the central dogma of molecular biology with access to individual genetic data (genomics), temporal changes in transcribed RNA (transcriptomics), and metabolic fingerprinting (metabolomics) from the same samples. Systems biology has gone a step further to account for the environmental impact on health and disease, giving rise to the emergence of nutriomics, phenomics, exomics, and the intense study of the microbiome. Continued proliferation in systems biology applications has resulted in increasing accessibility to affordable and rapid systems biology analytical platforms from which highly complex and multivariate datasets are being generated from a heterogeneous patient population, presenting a new challenge to precision medicine in the form of a data avalanche.

In response to the unique technological demands and opportunities presented by the surge in systems biology interest, scientists are faced with the challenge to deliver the step-change needed to deconvolve large-volume and complex datasets, examine their interplay with epidemiological factors, and inform medical practice from population-wide analyses in a timely manner. Deep learning (very broadly – iterative pattern analysis or classification using machine learning approaches) has emerged as a suite of powerful tools for modelling readout from such studies that involves integrating various data formats with electronic patient health records.

Beyond the lab, the rising star in technologies transforming precision medicine has been the increased utility of wearables and mobile applications enabling real-time and continuous accumulation of a wealth of physical health data outside the clinic. Lifestyle and fitness markets have been the driver for rapid uptake of wearables that have been repurposed for application in healthcare. Beyond measurement of primary vital signs, innovations in wearable analytical capabilities will enable future monitoring of clinically-relevant parameters in the management of chronic conditions.

For modern precision medicine to become a success requires large-scale harmonisation and standardisation of industry and academic sector practices in data acquisition, management and sharing methods to accommodate the demands of large-scale opportunities afforded by globalisation of biological datasets. In the technological race for attaining the holy grail of ‘off-the-shelf’ precision medicine products, those sectors and institutions unable to navigate the multi-faceted obstacles along the way will fall behind the curve of advancement at the expense of healthcare quality.

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Published: 25 Mar 2019
By Zahra Rattray, Nicholas Rattray

About the author

Zahra Rattray

Dr Zahra Rattray is a Chancellor’s fellow and lecturer at Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS). Her postdoctoral research and industry experience as senior scientist at AstraZeneca, has seen her contribute to a pharmacologically diverse project portfolio. Before taking up her current position at SIPBS, Zahra was a postdoctoral researcher at Yale University where she evaluated a lupus anti-DNA autoantibody for cancer treatment. Zahra’s lab focuses on using novel bioanalytical tools and translational approaches to studying oncology nanomedicine characteristics impacting there in vivo fate.

Nicholas Rattray

Dr Nicholas Rattray is also a Chancellor’s Fellow and Lecturer at SIPBS. He has over 10 years’ experience in mass spectrometry-based metabolomics and imaging mass spectrometry alongside advanced multivariate data analysis and epidemiological statistics. Having obtained his PhD from the Pharmacy School at the University of Manchester, he has developed a research direction in the metabolism of ageing from postdoctoral positions at the Manchester Institute of Biotechnology and Yale School of Public Health.

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