Statistical and integrative system-level analysis of DNA methylation data

Epigenetics plays a key role in cellular development and function. Alterations to the epigenome are thought to capture and mediate the effects of genetic and environmental risk factors on complex disease. Currently, DNA methylation is the only epigenetic mark that can be measured reliably and genome-wide in large numbers of samples. This Review discusses some of the key statistical challenges and algorithms associated with drawing inferences from DNA methylation data, including cell-type heterogeneity, feature selection, reverse causation and system-level analyses that require integration with other data types such as gene expression, genotype, transcription factor binding and other epigenetic information

Person-Centred Integrative Diagnosis: Conceptual Bases and Structural Model

Objectives: To review the conceptual bases of Person-centred Integrative Diagnosis (PID) as a component and contributor to person-centred psychiatry and medicine and to outline its design and development. Method: An analysis was conducted of the historical roots of person-centred psychiatry and medicine, tracing them back to ancient Eastern and Western civilizations, to the vicissitudes of modern medicine, to recent clinical and conceptual developments, and to emerging efforts to reprioritize medicine from disease to patient to person in collaboration with the World Medical Association, the World Health Organization, the World Organization of Family Doctors, the World Federation for Mental Health, and numerous other global health entities, and with the coordinating support of the International Network for Person-centered Medicine. Results: One of the prominent endeavours within the broad paradigmatic health development outlined above is the design of PID. This diagnostic model articulates science and humanism to obtain a diagnosis of the person (of the totality of the person's health, both ill and positive aspects), by the person (with clinicians extending themselves as full human beings), for the person (assisting the fulfillment of the person's health aspirations and life project), and with the person (in respectful and empowering relationship with the person who consults). This broader and deeper notion of diagnosis goes beyond the more restricted concepts of nosological and differential diagnoses. The proposed PID model is defined by 3 keys: broad informational domains, covering both ill health and positive health along 3 levels: health status, experience of health, and contributors to health; pluralistic descriptive procedures (categories, dimensions and narratives); and evaluative partnerships among clinicians, patients, and families. An unfolding research program is focused on the construction of a practical guide and its evaluation, followed by efforts to facilitate clinical implementation and training. Conclusions: PID is aimed at appraising overall health through pluralistic descriptions and evaluative partnerships, and leading through a research program to more effective, integrative, and person-centred health care.</p

Whole-genome bisulfite sequencing of goat skins identifies signatures associated with hair cycling

Abstract Background Hair follicles (HFs), upon development, undergo repetitive cycles of growth (anagen), regression (catagen), and rest (telogen). The transition between the stages is determined by multiple molecular signals, including DNA methylation, which plays important roles in mammalian cellular identity and is essential for the development of HFs. Secondary hair follicles (SHFs) in cashmere goat exhibit classic cyclic hair development, and little has been done on a genome-wide scale to examine potentially methylated genes involved in the hair cyclic transition. Results Genome-wide DNA methylation profiles between skin tissues sampled during the anagen and telogen stages in cashmere goats were investigated using whole-genome bisulfite sequencing (WGBS). The methylation status was observed to be higher in the skin samples with HFs in the telogen than those in the anagen stage. A total of 1311 differentially methylated regions (DMRs) were identified between the two groups, which contained 493 fully annotated DMR-related genes (DMGs) (269 Hyper- DMGs and 224 Hypo-DMGs). Furthermore, a significant over-representation of the functional categories for DMGs related to immune response and intercellular crosstalk during hair cycling was observed. By integrating DNA methylation and mRNA expression data, we revealed that four genes (FMN1, PCOLCE, SPTLC3, and COL5A1) are crucial factors for elucidating epigenetic mechanisms contributing to the telogen-to-anagen transition. Conclusion Our study provided systematic methylome maps pertaining to the hair cycling stages (anagen vs telogen) at a single-base resolution, and revealed stage-specific methylation loci during cashmere growth or quiescence. Furthermore, we identified epigenetically regulated genes that are potentially involved in HF development and growth in cashmere goats, and likely in other mammal species