Unlocking MENA's potential in rare-disease precision medicine.
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Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.
In this paper we present scientific advance in acupuncture based on electrical, neurophysiological, biochemical and therapeutic studies made inside and outside China since the early fifties. New modalities other than traditional needling techniques notably developed in Japan, France and Germany are described. For future prospects, efforts by making use of systems approach, field-body interaction, self-defense self-strategy and circadian rhythm are likely to produce great fruition in medicine. Possibilities of making advances in "three P's" medicine (preventive medicine, precision medicine and people medicine) by acupuncture are discussed.
Microgravity research has emerged as a rapidly evolving field at the intersection of space medicine, genomics, biotechnology, and precision medicine. Exposure to the space environment induces complex physiological and molecular adaptations that affect multiple biological systems, including immune regulation, metabolism, musculoskeletal function, and gene expression. Recent advances in genomics, multi-omics technologies, artificial intelligence, and bioengineering have substantially improved our understanding of biological adaptation to spaceflight and expanded opportunities for translational biomedical research. This review summarizes recent advances in genetic and biomedical research under microgravity conditions, with particular emphasis on molecular mechanisms, omics technologies, genome editing, microbiome research, regenerative medicine, and personalized healthcare approaches. Major experimental platforms, landmark spaceflight studies, and translational applications in infectious diseases, cancer biology, aging, tissue engineering, and pharmaceutical development are discussed. The review also highlights Saudi Arabia's emerging contributions to genomic medicine and space biosciences through initiatives such as the Saudi Human Genome Program, the Saudi Pangenome Project, the Saudi Space Agency, and the BioGravity Initiative. Recent Saudi participation in human spaceflight and microgravity-associated biomedical research is discussed within the context of Vision 2030 and national investments in biotechnology and precision medicine. Collectively, advances in microgravity research are expected to contribute to the advancement of precision medicine and facilitate the development of innovative diagnostic and therapeutic strategies with significant implications for both human space exploration and terrestrial healthcare.
Solid dispersions were prepared by the evaporation of ethanol after dissolving into ethanol a water soluble medicine (oxprenolol hydrochloride (OXP)), four grades of water insoluble ethylcellulose (EC) and four grades of water soluble hydroxypropyl cellulose (HPC), both having different molecular weights. The precise control of the release rat of a water soluble medicine by applying the difference in the molecular weight of polymers was attempted. The pore size distribution in solid dispersion granules was measured before and after the dissolution test by mercury intrusion porosimetry to clarify the mechanism of medicine release from the granules when the molecular weights of polymers were different. The state of medicine in the solid dispersions was analyzed by thermal analysis and X-ray diffractometry. Although the difference was slight, the release rate of OXP from the granules of the OXP-HPC system decreased as the molecular weight of HPC increased. The release behavior of OXP in the OXP-EC system was scarcely affected by the molecular weight of EC. However, in the OXP-EC-HPC system, the release rate markedly decreased with a larger molecular weight of EC. It was thought from the results of the pore size distribution that there were two types of release routes for OXP; dissolving directly into the dissolution medium and diffusing in the swelled HPC phase, caused by the addition of HPC. The decrease in the release rate of OXP in the OXP-EC-HPC system was caused by the increase in the ratio of OXP dissolving via the latter route, occurring with a larger molecular weight of EC. These results suggest that it is feasible to precisely control the release of a water soluble medicine by varying the molecular weight of the polymers in the solid dispersion.
PURPOSE: Precision medicine, also known as personalized medicine, enables the provision of tailored health services to patients. In the prevention, early detection, and treatment of cancers, precision medicine is highly promising, given the increasing use of genomic profiling for diagnosis and adapting therapies in several tumor types. Artificial Intelligence (AI) can support this process by analyzing vast amounts of relevant data. However, high-quality data and financial investments in the health system are essential for the implementation of precision medicine and AI solutions in routine cancer care. DESIGN/METHODOLOGY/APPROACH: Building on the quantitative outcomes of a foresight exercise published in another study, this article collects qualitative data to gain more detailed insights into the future of precision oncology in Belgium and discusses the role of AI in this field. It reports the results of a series of expert workshops, focusing on four hypothetical future scenarios that are centered around technological and economic issues that must be overcome for the widespread use of precision oncology in Belgium. FINDINGS: The study concludes that all four scenarios discussed in the workshops would require supportive policy measures in Belgium, which should go beyond mere technological and economic considerations, such as involving patient associations and the public in policy design or creating multi-disciplinary expert groups for precision medicine. ORIGINALITY/VALUE: To the best of our knowledge, this is the first study to employ foresight methodology to illustrate possible future scenarios, scrutinize feasible approaches for implementing precision oncology in Belgium, and discuss the use of AI in this context.
INTRODUCTION: When research fails to reach and engage all populations who might benefit from study findings, it can compromise scientific validity and ultimately health equity. Few studies have systematically examined factors driving study engagement through longitudinal intervention research. This project examined sociodemographic, geographic, and structural influences on engagement and attrition across the participation "cascade" (outreach, enrollment, retention) for two large-scale multilevel precision medicine and precision prevention trials for smoking and lung cancer screening. METHODS: Modified Poisson regression models were used to determine the factors associated with study engagement based on sociodemographic and geographical factors at each step in the cascade of participation, from initial outreach through retention at 12 months post-enrollment. Secondary analyses examined the cascade among the subset of patients who had active electronic patient portals and were approached via the portal. RESULTS: A total of 24,366 patients were approached for participation. Race, Social Vulnerability Index (SVI), insurance status, and distance from the study site were significantly associated with engagement at various points in the cascade. Black patients were more likely than White patients to be reached (48.9% vs 47.1%; p = 0.022) and to complete eligibility screening (52.8% vs. 38.4%; p < 0.001), but less likely to consent to participate (56.7% vs 69.8%; p < 0.001) and complete genetic testing (58.5% vs. 69.8%; p = 0.003). Patterns of engagement through electronic patient portal versus non-electronic recruitment channels also differed by race- and place-based factors, with Black patients being less likely than White patients to respond in the portal (8.8% vs 15.5%; p < 0.001), and patients who reside farther from the study site being more likely to respond in the portal compared to those who live closer (14.9% vs 12.5%; p < 0.001). CONCLUSIONS: These findings highlight the need for tailored, stage-specific engagement strategies to ensure representative participation in genomic and behavioral intervention research to advance the integration of genomics into public health practice.
Human genome research which tries to map and sequence all the 3 billion nucleotides in the entire DNA is progressing rapidly. Completion of the human genome sequencing is expected before the year 2005. Human genes, totalling 50,000-100,000, will be identified, allowing the complete set of proteins--'the proteome' to be known. This together with genomic research in other species will lead to complete understanding of life at the molecular level and also its evolutionary history of 3,500 million years. Genomics will bring about a revolution in biology and health, because it is equivalent to having a 'Biological Periodic Table' which is a foundation for understanding life, health, disease and for deriving of new tools for diagnosis, treatment, prognosis and prevention. Human genomics will give rise to Predictive--Preventive Medicine and Precision Medicine. It will have profound social implications. Preparation for the future is needed for societies to cope with and make proper use of the tremendous changes to be brought about by genomics.
INTRODUCTION: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and the MET exon 14 skipping mutation is a key oncogenic driver, which promotes tumor progression and provides a new direction for precision therapy. METHODS: A systematic search of English-language literature and clinical trial data related to the MET exon 14 skipping mutation from 2020-2025 was performed to summarize the role of the mutation and therapeutic advances. RESULTS: DNA-based next-generation sequencing (NGS), RNA-based NGS, and RT-qPCR were employed as the main detection methods. Preclinical models confirmed that mutations promote tumor progression by activating the RAS/MAPK pathway. Clinical trials have reported objective remission rates (ORR) of 46-68% for first-line treatment with MET inhibitors in NSCLC patients harboring MET exon 14 skipping mutations. DISCUSSION: MET exon 14 skipping mutation as a therapeutic target for NSCLC has made significant progress, and MET inhibitors are more advantageous than chemotherapy and immunotherapy, and have been recommended by national and international guidelines as a first-line treatment option. Additionally, NGS technology has the potential to dynamically monitor tumor evolution and drugresistant mutations, thereby helping to realize precision medicine. CONCLUSION: The MET exon 14 skipping mutation is an important target for the precision treatment of NSCLC, and MET-TKIs have remarkable efficacy but a prominent problem with drug resistance. The construction of a precision medicine system encompassing diagnosis, treatment, and drug resistance management through multi-omics research, technological innovation, and international collaboration is a key direction for improving prognosis.
MOTIVATION: Precision medicine leverages patient-specific multimodal data to improve prevention, diagnosis, prognosis, and treatment of diseases. Advancing precision medicine requires the non-trivial integration of complex, heterogeneous, and potentially high-dimensional data sources, such as multi-omics and clinical data. In the literature, several approaches have been proposed to manage missing data, but are usually limited to the recovery of subsets of features for a subset of patients. A largely overlooked problem is the integration of multiple sources of data when one or more of them are completely missing for a subset of patients, a relatively common condition in clinical practice. RESULTS: We propose miss-Similarity Network Fusion (miss-SNF), a novel general-purpose data integration approach designed to manage completely missing data in the context of patient similarity networks. miss-SNF integrates incomplete unimodal patient similarity networks by leveraging a non-linear message-passing strategy borrowed from the SNF algorithm. miss-SNF is able to recover missing patient similarities and is "task agnostic", in the sense that can integrate partial data for both unsupervised and supervised prediction tasks. Experimental analyses on nine cancer datasets from The Cancer Genome Atlas (TCGA) demonstrate that miss-SNF achieves state-of-the-art results in recovering similarities and in identifying patients subgroups enriched in clinically relevant variables and having differential survival. Moreover, amputation experiments show that miss-SNF supervised prediction of cancer clinical outcomes and Alzheimer's disease diagnosis with completely missing data achieves results comparable to those obtained when all the data are available. AVAILABILITY AND IMPLEMENTATION: miss-SNF code, implemented in R, is available at https://github.com/AnacletoLAB/missSNF.
Alzheimer's disease (AD) is characterized by region- and patient-specific molecular heterogeneity, which hinders therapeutic design. In this study, we introduce PRISM-ML (PRecision-medicine using Interpretable Systems and Multiomics with Machine Learning), an open-source integrated analysis pipeline that combines interpretable machine learning with systems biology and electronic health records data mining to elucidate the molecular diversity of AD and predict promising drug repurposing opportunities. First, we integrated and harmonized transcriptomic (bulk RNA-seq) and genomic (genome-wide association study) data from 2105 brain samples, each with matched data from the same individual (1363 AD patients, 742 controls; 9 tissues), sourced from three independent studies. Random forest classifiers with SHapley Additive exPlanations identified patient-specific biomarkers; unsupervised clustering resolved 36 molecularly distinct subtissues (defined as clusters of samples within a brain tissue that share a specific expression pattern); and gene-gene coexpression networks prioritized 262 high-centrality bottleneck genes as putative regulators of dysregulated pathways. Next, knowledge graph-based drug repurposing predicted six Food and Drug Administration (FDA)-approved drugs that simultaneously target multiple bottleneck genes and multiple AD-relevant pathways. Notably, in a large US de-identified insurance-claims database (n = 364 733), exposure to promethazine, one of the candidate drugs, was associated with a 57%-62% lower incidence of AD versus an active antihistamine comparator (adjusted hazard ratio 0.38; inverse-probability weighted 0.43; both P < .001), providing real-world support for its repurposing potential. In summary, PRISM-ML, as an explainable multiomics analysis pipeline, is readily transferable to other complex diseases, advancing precision medicine.
Diabetes mellitus encompasses several disorders, each with differing clinical presentation, prognoses and pathophysiology. Distinct polygenic architectures underlie type 1 diabetes mellitus and type 2 diabetes mellitus, and govern numerous pathophysiological pathways that converge on dysglycaemia. Over the previous decade, polygenic risk scores (PRS) derived from large genome-wide association studies have become broadly recognized for their potential in precision medicine. PRS, and now partitioned polygenic scores generated by clustering of risk variants, can quantify individual genetic predisposition to diabetes mellitus and reveal molecular heterogeneity responsible for variation in clinical presentation and prognoses. In this Review, we examine and contrast progress in the development of type 1 diabetes mellitus PRS and type 2 diabetes mellitus PRS, and discuss paths to further methodological advances. We examine how studies in the past 10 years have harnessed PRS and novel partitioned polygenic scores to reveal insights into diabetes mellitus aetiology and characterize changes in cellular and tissue-specific disease-modifying molecular pathways. Additionally, we discuss advances and opportunities in areas of clinical translation, including improved classification of diabetes mellitus type, screening of those at risk and personalized interventions informed by PRS. Finally, we emphasize the urgent need to overcome ancestry-related challenges and highlight current progress and gaps in ensuring the equitable translation of PRS for diabetes mellitus precision medicine.
National genome projects (NGPs) are increasingly shaping precision medicine by improving representation of population-specific genetic diversity. This review compiles findings from NGPs across Asia and Africa, regions that remain underrepresented in global genomic databases despite their extensive demographic and genetic diversity. A total of 53 studies from 24 countries were identified to understand (1) the genomic approach utilized, (2) novel findings that have emerged, and (3) strategies for improving research in these regions. The NGPs implement population-based variome databases (20 NGPs), linear reference genome assemblies (8 NGPs), and graph-based pangenome assemblies (1 NGP). Novel variants ranged between 0.28% (China) and 19.6% (Iran), whereas rare variants accounted for up to 88.9% of the detected variants in the Chinese population. Each NGP documents its country's evolutionary and migration history, which impacts disease frequency and pharmacogenomic variants. Clinically, NGPs revealed strong population stratification in disease-associated and pharmacogenomic variants. For example, the GJB2 rs72474224 hearing-loss variant ranged from 13% in Vietnam and 12% in Hong Kong to 0.0894% in Turkey, while the VKORC1 rs9923231 pharmacogenomic variant reached 89.2% in Taiwan but was 20%-25% in European-related Russian subpopulations. These findings demonstrate that clinically relevant allele frequencies, pathogenicity assessments, and drug-response markers differ substantially across ancestries. This review highlights ongoing efforts and strategies to enhance the representativeness of genomic data through NGPs in Asia and Africa. We also suggest future directions for national projects, including integrating family-based studies, multi-omic data, and standardized pipelines to accelerate discovery and support the equitable implementation of precision medicine.
BACKGROUND/OBJECTIVES: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with significant racial and ethnic disparities in incidence, tumor biology, and clinical outcomes. Hispanic/Latino (H/L) patients tend to be diagnosed at younger ages and more advanced stages than Non-Hispanic White (NHW) patients, yet the molecular mechanisms underlying these disparities remain poorly understood. Key oncogenic pathways, including RTK/RAS, TGF-Beta, WNT, PI3K, and TP53, play pivotal roles in tumor progression, treatment resistance, and response to targeted therapies. However, ethnicity-specific alterations within these pathways remain largely unexplored. This study aims to compare pathway-specific mutations in HCC between H/L and NHW patients, assess tumor mutation burden, and identify ethnicity-associated oncogenic drivers using publicly available datasets. Findings from this analysis may inform precision medicine strategies for improving early detection and targeted therapies in underrepresented populations. METHODS: We conducted a bioinformatics analysis using publicly available HCC datasets to assess mutation frequencies in RTK/RAS, TGF-Beta, WNT, PI3K, and TP53 pathway genes. The study included 547 patients, consisting of 69 H/L patients and 478 NHW patients. Patients were stratified by ethnicity (H/L vs. NHW) to evaluate differences in mutation prevalence. Chi-squared tests were used to compare mutation frequencies, while Kaplan-Meier survival analysis assessed overall survival differences associated with pathway-specific alterations in both populations. RESULTS: Significant differences were observed in the RTK/RAS pathway related genes, particularly in FGFR4 mutations, which were more prevalent in H/L patients compared to NHW patients (4.3% vs. 0.6%, p = 0.02). Additionally, IGF1R mutations exhibited borderline significance (7.2% vs. 2.9%, p = 0.07). In the PI3K pathway, INPP4B alterations were more frequent in H/L patients than in NHW patients (4.3% vs. 1%, p = 0.06), while in the TGF-Beta pathway, TGFBR2 mutations were more common in H/L patients (2.9% vs. 0.4%, p = 0.07), suggesting potential ethnicity-specific variations. Survival analysis revealed no significant differences in overall survival between H/L and NHW patients, indicating that molecular alterations alone may not fully explain survival disparities and suggesting a role for additional factors such as immune response, environmental exposures, or access to targeted therapies. CONCLUSIONS: This study provides one of the first ethnicity-focused analyses of key oncogenic pathway alterations in HCC, revealing distinct molecular differences between H/L and NHW patients. The findings suggest that RTK/RAS (FGFR4, IGF1R), PI3K (INPP4B), and TGF-Beta (TGFBR2) pathway alterations may play a distinct role in HCC among H/L patients, while their prognostic significance in NHW patients remains unclear. These insights emphasize the importance of incorporating ethnicity-specific molecular profiling into precision medicine approaches to improve early detection, targeted therapies, and clinical outcomes in HCC, particularly for underrepresented populations.
IMPORTANCE: Single gene variants can cause cerebral palsy (CP) phenotypes, yet the impact of genetic diagnosis on CP clinical management has not been systematically evaluated. OBJECTIVE: To evaluate how frequently genetic testing results would prompt changes in care for individuals with CP and the clinical utility of precision medicine therapies. DATA SOURCES: Published pathogenic or likely pathogenic variants in OMIM genes identified with exome sequencing in clinical (n = 1345) or research (n = 496) cohorts of CP were analyzed. A systematic literature review for evidence of effective therapies for specific genetic etiologies was performed. STUDY SELECTION: Nonstandard interventions that led to a detectable improvement in a defined outcome in individuals with variants in the gene of interest were included. DATA EXTRACTION AND SYNTHESIS: Literature was evaluated using PRISMA guidelines. A diverse, expert working group was established, scoring rubrics adapted, and scoring consensus built with a modified Delphi approach. MAIN OUTCOMES AND MEASURES: Overall clinical utility was calculated from metrics assessing outcome severity if left untreated, safety and practicality of the intervention, and anticipated intervention efficacy on a scale from 0 to 3. RESULTS: Of 1841 patients with CP who underwent exome sequencing, 502 (27%) had pathogenic or likely pathogenic variants related to their phenotype. A total of 243 different genes were identified. In 1841 patients with identified genetic etiologies of CP, 140 (8%) had a genetic etiology classified as actionable, defined as prompting a change in clinical management. Also identified were 58 of 243 genes with pathogenic or likely pathogenic variants with actionable treatment options: 16 targeting the primary disease mechanism, 16 with specific prevention strategies, and 26 with specific symptom management. The level of evidence was also graded according to ClinGen criteria; 45 of 101 interventions (44.6%) had evidence class D or below. The potential interventions have clinical utility with 98 of 101 outcomes (97%) being moderate-high severity if left untreated and 63 of 101 interventions (62%) predicted to be of moderate-high efficacy. Most interventions (72 of 101 [71%]) were considered moderate-high safety and practicality. CONCLUSIONS AND RELEVANCE: The findings indicate that actionable genetic findings occurred in 8% of individuals referred for genetic testing with CP. Evaluation of potential efficacy, outcome severity, and intervention safety and practicality indicates moderate-high clinical utility of these genetic findings. Genetic sequencing can identify precision medicine interventions that provide clinical benefit to individuals with CP. The relatively limited evidence base underscores the need for additional research.
PURPOSE: Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS: Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS: Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub (P < .05 for all). CONCLUSION: White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.
PURPOSE: This descriptive qualitative study explored knowledge users' perspectives on precision rehabilitation concepts, barriers, facilitators, and future directions as part of a convergent mixed methods scoping review. MATERIALS AND METHODS: Sixteen clinicians, administrators, and researchers from three North American tertiary care rehabilitation centers were recruited using convenience and snowball sampling to participate in individual semi-structured interviews. Conventional qualitative content analysis followed a deductive thematic approach based on predetermined categories. RESULTS: Analyses revealed three main themes: (1) Although precision rehabilitation shares foundational concepts with precision medicine, there are certain elements, such as personalization, that are uniquely expressed; (2) Rehabilitation-specific facilitators to precision approaches include the use of unobtrusive technology to collect large amounts of data in real-world contexts, while barriers include rehabilitation's typically small, heterogeneous sample sizes; and (3) The future of precision rehabilitation will require collaborative data-sharing to focus on determining care trajectories that enhance functional outcomes. CONCLUSION: Findings provide the first qualitative synthesis of knowledge users perspectives to complement quantitative evidence and inform the emerging field of precision rehabilitation.
Organoids, three-dimensional cell culture models derived from patient tissues or stem cells, have emerged as a cutting-edge technology in personalized medicine, owing to their remarkable ability to closely recapitulate in vivo tissue architecture and function. This review provides a comprehensive overview of the technological evolution and construction methodologies of organoids, highlighting their significant applications in oncology, genetic disorders, infectious diseases, and drug screening. This review examines how organoids enable precision medicine by preserving genomic fidelity, predicting drug sensitivity, and creating disease models via gene editing. Despite these advances, organoid technology faces several technical challenges that impede its full clinical translation. Addressing these obstacles is critical for realizing the potential of organoids in individualized therapeutic strategies. This article aims to delineate current progress and future directions in organoid research, furnishing a theoretical foundation and guiding future investigations towards enhancing personalized treatment paradigms.