Phenotyping: Targeting genotype's rich cousin for diagnosis

Abstract

There are many current and evolving tools to assist clinicians in their daily work of phenotyping. In medicine, the term 'phenotype' is usually taken to mean some deviation from normal morphology, physiology and behaviour. It is ascertained via history, examination and investigations, and a primary aim is diagnosis. Therefore, doctors are, by necessity, expert 'phenotypers'. There is an inherent and partially realised power in phenotypic information that when harnessed can improve patient care. Furthermore, phenotyping developments are increasingly important in an era of rapid advances in genomic technology. Fortunately, there is an expanding network of phenotyping tools that are poised for clinical translation. These tools will preferentially be implemented to mirror clinical workflows and to integrate with advances in genomic and information-sharing technologies. This will synergise with and augment the clinical acumen of medical practitioners. We outline key enablers of the ascertainment, integration and interrogation of clinical phenotype by using genetic diseases, particularly rare ones, as a theme. Successes from the test bed or rare diseases will support approaches to common disease.

Exploring the Underlying Genetics of Craniofacial Morphology through Various Sources of Knowledge

“…Approximately 32% of the inherited human disorders are associated with atypical craniofacial characteristics [20–22]. These “face signatures” (i.e., the face shape difference normalized against age and sex matched controls) can provide the additional clues for clinical diagnoses of genetic syndromes [23, 24]. …”

“…The term “phenotype” in a clinical setting is often used to indicate characteristics that are deviating from the “normal” or typical morphology, physiology, and behavior [24]. This gives rise to questions of what is typical.…”

Why Are Omics Technologies Important to Understanding the Role of Nutrition in Inflammatory Bowel Diseases?

“…Proteomics has been defined as “the analysis of the protein complement present in a cell, organ, or organism at any given time [55]”.…”

“…Proteins and/or peptides are generally separated out through gel electrophoresis or liquid chromatography, both of which can be either one- or two-dimensional, and are typically coupled with mass spectrometry. A comprehensive description of current technologies for a proteomics approach to the assessment of biological samples has been published relatively recently [55]. …”

Phelan‐McDermid syndrome data network: Integrating patient reported outcomes with clinical notes and curated genetic reports

“…Research investigations using Genome Wide Association Study (GWAS) (Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, 2015; Wood, 2013), exome‐based sequencing (Girard et al, 2011; Iossifov et al, 2012; O'Roak et al, 2011; Vissers et al, 2010; Xu et al, 2012), and whole genome sequencing (Kong et al, 2012) techniques have revealed several candidate genes that are associated with common neuropsychiatric disorders such as Autism Spectrum Disorder (ASD), intellectual disability, and schizophrenia. However, in the case of rare disorders, understanding the genetic origins and progressions of disorders—one of the key objectives of Precision Medicine research (Collins & Varmus, 2015; Kohane, 2015; Kohane, Churchill, & Murphy, 2012)—is hindered by small patient population size, the consequent paucity of patient data, and the lack of robust phenotyping protocols (Baynam et al, 2015; Delude, 2015; Robinson, Mungall, & Haendel, 2015). …”