The second decade of the twenty-first century has witnessed a surging interest in personalized medicine with the concomitant promise to enable more precise diagnosis and treatment of disease and ...illness, based upon an individual’s unique genetic makeup.In this book, my goal is to contribute to a growing body of literature on personalized medicine by tracing and analyzing how this field has blossomed in Asia. In so doing, I aim to illustrate how various social and economic forces shape the co-production of science and social order in global contexts. This book shows that there are inextricable transnational linkages between developing and developed countries and also provides a theoretically guided and empirically grounded understanding of the formation and usage of particular racial and ethnic human taxonomies in local, national and transnational settings.
The omics era has greatly expanded the repertoire of approaches available for researchers and clinicians to unravel the complexity underpinning human health: Next Generation Sequencing (NGS) ...approaches can characterize genomes, epigenomes, transcriptomes and proteomes. The analyses are critical to assess in individuals both pre- and post-treatment during therapeutic development and early-stage clinical trials. Peripheral blood mononuclear cells (PBMCs) offer a non-invasive approach that, when combined with omics tools, can provide a near holistic view of immune processes across patient cohorts. Meanwhile, Formalin Fixed Paraffin Embedded (FFPE) tissues are a staple in clinical diagnostics and an ideal means to store archival tissue but can be difficult to work with in traditional NGS assays.
Here we detail workflows using both fresh and fixed patient samples to rapidly produce a diverse set of multiomics results including genomics, epigenomics, transcriptomics and proteomics. For fresh blood draws, this starts with automated sample handling and processing to ensure high viability and yield of PBMCs, along with simultaneous plasma separation and collection. Samples are then aliquoted and simultaneously processed for whole exome sequencing, single cell RNA sequencing, epigenetic characterization and Olink biomarker analysis. For fixed tissues, FFPE blocks were serially sliced into various FFPE slides, with a single slide H&E stained. Individual slides were then utilized for genome, epigenome, single cell RNA-seq, and digital spatial profiling. Genome information was captured using hybrid capture based approaches followed by deep NGS on an Illumina platform and analyzed for a variety of variants and tumor mutational burden. DNA methylation was detailed using target capture probes targeting DNA methylation sites. Single cell approaches were applied to explore the transcriptome using 10X Genomics scRNAseq kit, and Digital Spatial Profiling (DSP) was done using the NanoString GeoMx® Whole Transcriptome Atlas and immunostaining.
With these robust workflows, all these datatypes can be produced within days of fresh or fixed sample receipt using minimal sample amounts. High throughput integrative omics workflows, as described here, drive greater insights in human health, allowing for a rapid combined approach to address the biological questions at hand.
Organoids are in vitro-cultured three-dimensional structures that recapitulate key aspects of in vivo organs. They can be established from pluripotent stem cells and from adult stem cells, the latter ...being the subject of this review. Organoids derived from adult stem cells exploit the tissue regeneration process that is driven by these cells, and they can be established directly from the healthy or diseased epithelium of many organs. Organoids are amenable to any experimental approach that has been developed for cell lines. Applications in experimental biology involve the modeling of tissue physiology and disease, including malignant, hereditary, and infectious diseases. Biobanks of patient-derived tumor organoids are used in drug development research, and they hold promise for developing personalized and regenerative medicine. In this review, we discuss the applications of adult stem cell-derived organoids in the laboratory and the clinic.
In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in ...fact, angina.
This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI).
ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from −10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI.
Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr(difference) >99.9%.
Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization ORBITA-STAR; NCT04280575)
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Personalized Models of Psychopathology Wright, Aidan G.C; Woods, William C
Annual review of clinical psychology,
05/2020, Volume:
16, Issue:
1
Journal Article
Peer reviewed
Open access
The personalized approach to psychopathology conceptualizes mental disorder as a complex system of contextualized dynamic processes that is nontrivially specific to each individual, and it seeks to ...develop formal idiographic statistical models to represent these individual processes. Although the personalized approach draws on long-standing influences in clinical psychology, there has been an explosion of research in recent years following the development of intensive longitudinal data capture and statistical techniques that facilitate modeling of the dynamic processes of each individual's pathology. Advances are also making idiographic analyses scalable and generalizable. We review emerging research using the personalized approach in descriptive psychopathology, precision assessment, and treatment selection and tailoring, and we identify future challenges and areas in need of additional research. The personalized approach to psychopathology holds promise to resolve thorny diagnostic issues, generate novel insights, and improve the timing and efficacy of interventions.
Machine learning approaches for clinical psychology and psychiatry explicitly focus on learning statistical functions from multidimensional data sets to make generalizable predictions about ...individuals. The goal of this review is to provide an accessible understanding of why this approach is important for future practice given its potential to augment decisions associated with the diagnosis, prognosis, and treatment of people suffering from mental illness using clinical and biological data. To this end, the limitations of current statistical paradigms in mental health research are critiqued, and an introduction is provided to critical machine learning methods used in clinical studies. A selective literature review is then presented aiming to reinforce the usefulness of machine learning methods and provide evidence of their potential. In the context of promising initial results, the current limitations of machine learning approaches are addressed, and considerations for future clinical translation are outlined.
Background & Aims: There is great current interest in the potential application of DNA methylation alterations in peripheral blood leukocytes (PBLs) as biomarkers of susceptibility, progression, and ...treatment response in inflammatory bowel disease (IBD). However, the intra-individual stability of PBL methylation in IBD has not been characterized. Here, we studied the long-term stability of all probes located on the Illumina HumanMethylation EPIC BeadChip array. Methods: We followed a cohort of 46 adult patients with IBD (36 Crohn’s disease CD, 10 ulcerative colitis UC; median age, 44 years; interquartile range IQR 27–56 years; 50% female) that received standard care follow-up at the Amsterdam University Medical Centers. Paired PBL samples were collected at 2 time points with a median of 7 years (range, 2–9 years) in between. Differential methylation and intra-class correlation (ICC) analyses were used to identify time-associated differences and temporally stable CpGs, respectively. Results: Around 60% of all EPIC array loci presented poor intra-individual stability (ICC <0.50); 78.114 (≈9%) showed good (ICC, 0.75–0.89), and 41.274 (≈5%) showed excellent (ICC ≥0.90) stability, between both measured time points. Focusing on previously identified consistently differentially methylated positions indicated that 22 CD-, 11 UC-, and 24 IBD-associated loci demonstrated high stability (ICC ≥0.75) over time; of these, we observed a marked stability of CpG loci associated to the HLA genes. Conclusions: Our data provide insight into the long-term stability of the PBL DNA methylome within an IBD context, facilitating the selection of biologically relevant and robust IBD-associated epigenetic biomarkers with increased potential for independent validation. These data also have potential implications in understanding disease pathogenesis.
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