This is now possible because of the enormous amount of detailed information – or data - that we have about the genes and proteins in patients’ single cells and tissues (bioinformatics), and the wealth of key routinely collected heath data within comprehensive electronic healthcare records (health informatics). Bringing this informatics spectrum together provides an incredible powerful tool both for clinical research and for improving health outcomes.
This theme thus focuses on joining up bioinformatics with health informatics to develop new ways of delivering precision care in diseases that often affect older individuals. Some of these are relatively common such as arthritis, cancer and chronic inflammatory bowel disease, while others are so-called rare diseases, such as giant cell arteritis (inflammation of the arteries), a disorder that can cause blindness. We will use the information from individual diseases to understand how they interact in people with multiple long-term conditions and use precision care to improve the treatment of individual patients.
Artificial intelligence (AI) will be used to identify the interactions between microscopic and sub-microscopic patient characteristics, their co-existing diseases, and their treatments, and to select sub-groups of patients who are most likely to benefit from new treatments in clinical trials. In short, we intend to go from cells, to patients, to populations, and then back to individual patients, to select the most appropriate patients for future clinical trials.
Several groups in Newcastle are already using sophisticated methods to extract data from single cells about their genes and the regulation of their biological processes. They have worked with bioinformatics experts to understand how normal cells function, and what goes wrong in diseases. Our studies will extend this to further develop bioinformatics to enable earlier diagnoses and better predict outcomes (prognoses) of diseases.
Members of the IPCAP Theme at their Annual Strategy meeting in December 2024
At the other end of the informatics pathway, we are also in a strong position because we have developed an ethically-approved information governance framework, and computer systems to use anonymised healthcare data from The Newcastle upon Tyne NHS Foundation Trust’s digital patient records, and the development of a comprehensive health information exchange for direct patient care, the Great North Care Record, and which now feeds into the new North East and North Cumbria Secure Data Environment which covers all primary, secondary and tertiary NHS care across the North East and North Cumbria.
We are fortunate to already have excellent informaticians that are contributing to the success of this work, but one of our goals is to build further capacity in both bioinformatics and health informatics. This is including the appointment of new staff to achieve the necessary critical mass, but also include an element of ‘upskilling’ – training clinical researchers in informatics and AI, and increasing the understanding of our colleagues in computing science and engineering about the importance of this work in precision care.
Authors:Alivernini S, Cañete JD, Bacardit J, Kurowska-Stolarska M.
Abstract: Current treatments for rheumatoid arthritis aim to achieve and maintain disease remission, which is characterized by the absence of symptoms of inflammation. However, remission is often fragile, with about 50% of patients experiencing disease flares after reducing or stopping medication, representing a burden for both patients and clinicians. Although some predictors of flare exist, they do not confidently predict flare for most patients with rheumatoid arthritis in remission. Recent studies suggest that deconvolution of patients’ synovial tissue cellular and molecular signatures may offer more accurate prediction models.
Nat Med 2024 Apr;30(4):925-926
doi: 10.1038/s41591-024-02818-w
PMID: 38361121
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Authors:Iyer JS, Juyal D, Le Q, Shanis Z, Pokkalla H, Pouryahya M, Pedawi A, Stanford-Moore SA, Biddle-Snead C, Carrasco-Zevallos O, Lin M, Egger R, Hoffman S, Elliott H, Leidal K, Myers RP, Chung C, Billin AN, Watkins TR, Patterson SD, Resnick M, Wack K, Glickman J, Burt AD, Loomba R, Sanyal AJ, Glass B, Montalto MC, Taylor-Weiner A, Wapinski I, Beck AH.
Abstract:Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ = 1) and aligned with expert pathologist consensus scores (κ = 0.62–0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P < 0.0001) and stage 4 (P = 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P = 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.
Nat Med 2024 Oct;30(10):2914-2923
doi: 10.1038/s41591-024-03172-7
Epub 2024 Aug 7
PMID: 39112795
PMCID: PMC11485234
Authors:Vaskimo LM, Gomon G, Naamane N, Cordell HJ, Pratt A, Knevel R
Abstract:Modest effect sizes have limited the clinical applicability of genetic associations with rheumatic diseases. Genetic risk scores (GRSs) have emerged as a promising solution to translate genetics into useful tools. In this review, we provide an overview of the recent literature on GRSs in rheumatic diseases. We describe six categories for which GRSs are used: (a) disease (outcome) prediction, (b) genetic commonalities between diseases, (c) disease differentiation, (d) interplay between genetics and environmental factors, (e) heritability and transferability, and (f) detecting causal relationships between traits. In our review of the literature, we identified current lacunas and opportunities for future work. First, the shortage of non-European genetic data restricts the application of many GRSs to European populations. Next, many GRSs are tested in settings enriched for cases that limit the transferability to real life. If intended for clinical application, GRSs are ideally tested in the relevant setting. Finally, there is much to elucidate regarding the co-occurrence of clinical traits to identify shared causal paths and elucidate relationships between the diseases. GRSs are useful instruments for this. Overall, the ever-continuing research on GRSs gives a hopeful outlook into the future of GRSs and indicates significant progress in their potential applications.
Genes (Basel) 2023 Dec 1;14(12):2167
doi: 10.3390/genes14122167
PMID: 38136989
PMCID: PMC10743278
Author:Lamb CA, Titterton C, Banerjee R, Gomberg A, Rubin DT, Hart AL.
Abstract:World inflammatory bowel disease (IBD) Day 2024 unites around the theme IBD has no borders. As a multinational authorship of physicians and people with lived experiences of IBD, we recognise that Crohn's disease and ulcerative colitis extend across both geographical and personal boundaries. Traditionally considered to be a disease of high-income countries (HICs), IBD today is a global condition with an accelerated incidence in Asia, Africa, and Latin America, which parallels industrialisation and lifestyle change. A compounded IBD prevalence in North America, Europe, and Australasia will reach 1 in 100 by the end of this decade. The people who have IBD today are diverse, of multiple races and cultures, with varying genetic make-up, and from different socioeconomic environments. These changes have uncovered barriers to equitable health-care access, especially in low-resource settings.
Lancet 2024 Aug 3;404(10451):414-417
Epub 2024 May 17
doi: 10.1016/S0140-6736(24)00983-8
PMID: 38768627
Author:Milne-Ives M, Riccalton V, Plummer C, Threlfall L, Cong C, Ananthakrishnan A, Meinert E.
Abstract:The National Early Warning Score (NEWS/2) system was developed to enable the detection and early intervention of patients at risk of clinical deterioration. It has demonstrated good accuracy in identifying imminent critical outcomes but has limitations in its applicability to various patient types and its ability to predict upcoming deterioration beyond 24 hours. Various studies have attempted to improve its predictive accuracy and clinical utility by modifying or adding variables to the standard NEWS/2 system. The purpose of this scoping review is to identify modifications to the NEWS and NEWS2 systems (eg, the inclusion of additional patient demographic, physiological or other characteristics) and how those modifications influence predictive accuracy to provide an evidence base for subsequent improvement of the system.
BMJ Open 2024 Oct 9;14(10):e089061
doi: 10.1136/bmjopen-2024-089061
PMID: 39384239
PMCID: PMC11474849
Theme Co-Lead for the Informatics and Precision Care for an Ageing Population and Professor of Precision & Molecular Pathology
Theme Co-Lead for the Informatics and Precision Care for an Ageing Population Theme, Digital Academic Lead, Honorary Senior Lecturer, Consultant Cardiologist and Chief Clinical Information Officer, NuTH
BRC Leadership Track for Informatics and Precision Care for an Ageing Population and PPIE Theme Lead, and Professor of Gastroenterology & Honorary Consultant in Gastroenterology
BRC Leadership Track for Informatics and Precision Care for an Ageing Population and Honorary Senior Lecturer, Consultant in Acute Medicine