Commercially available industry-relevant software in the education of genome variant curation

BACKGROUND Genome analytics is a drastically expanding field, and there is an increasing demand for individuals with the necessary skillset to analyse the genome data that is being generated. A new Masters by coursework was developed to train individuals in genome analytics. Institutions analysing genomes commonly utilise in-house analysis tools, but increasingly commercial software packages that integrate AI are being considered in the research and diagnostic space (De La Vega et al., 2021). AIMS Evaluate the effectiveness of commercially available software as a tool for teaching variant analysis, classification and curation, enabling the analysis of real-world case examples for the teaching, training and assessment of students in the field of diagnostic genome analysis.   Assess students’ perspectives on work readiness after using commercially available tools in the educational environment. DESIGN AND METHODS Students were exposed to the use and limitations of a commercial software package for Human genome curation during two core units of the course. This software was used as part of both in-class training and in their assessment case studies. Students were invited to voluntarily complete an online survey including qualitative and quantitative components featuring Likert scale questions, both pre and post exposure to the software. Paired data from 23 individuals (73% response rate), most aged between 18 and 25, were recorded and anonymised prior to analysis. Qualitative data were thematically coded blind by two individuals independently using emergent coding (Charmaz, 2008). RESULTS AND CONCLUSIONS This project indicates that after the completion of the units that integrated commercially available industry software, we measured increased student confidence (increase in percentage reporting fairly confident or higher) in joining the genetic analysis workforce (significant change from 37% to 70%) and in completing job-specific tasks (significant increase in 7 out of 9 tasks of between 28% to 39%). The aspects of their studies the students valued in relation to these changes and their perception of the usefulness of integration of the commercial software were elucidated from qualitative theming, and can inform others looking to integrate commercially available software within their tertiary degree. REFERENCES Charmaz, K. (2008).  Grounded theory as an emergent method. In S. N. Hesse-Biber & P. Leavy (Eds.), Handbook of emergent methods. (pp. 155-170). The Guilford Press.  De La Vega, F.M., Chowdhury, S., Moore, B., Frise, E., McCarthy, J., Hernandez, E.J., Wong, T., James, K., Guidugli, L., Agrawal, P.B., Genetti, C.A., Brownstein, C.A., Beggs, A.H., Löscher, B.S., Franke, A., Boone, B., Levy, S.E., Õunap, K., Pajusalu, S., … Kingsmore, S.F. (2021). Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases. Genome Med, 13(1), 153. https://doi.org/10.1186/s13073-021-00965-

EMQN:Recommendations for genetic testing in inherited cardiomyopathies and arrhythmias

Inherited cardiomyopathies and arrhythmias (ICAs) are a prevalent and clinically heterogeneous group of genetic disorders that are associated with increased risk of sudden cardiac death and heart failure. Making a genetic diagnosis can inform the management of patients and their at-risk relatives and, as such, molecular genetic testing is now considered an integral component of the clinical care pathway. However, ICAs are characterised by high genetic and allelic heterogeneity, incomplete / age-related penetrance, and variable expressivity. Therefore, despite our improved understanding of the genetic basis of these conditions, and significant technological advances over the past two decades, identifying and recognising the causative genotype remains challenging. As clinical genetic testing for ICAs becomes more widely available, it is increasingly important for clinical laboratories to consolidate existing knowledge and experience to inform and improve future practice. These recommendations have been compiled to help clinical laboratories navigate the challenges of ICAs and thereby facilitate best practice and consistency in genetic test provision for this group of disorders. General recommendations on internal and external quality control, referral, analysis, result interpretation, and reporting are described. Also included are appendices that provide specific information pertinent to genetic testing for hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathies, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.</p

Suggested actions from the Melbourne HVP Information Seminar

The Human Variome Project (HVP; www.humanvariomeproject.org) was initiated at a meeting in June 2006 and addressed the problems of collecting genetic information and generated 96 recommendations (http://www.nature.com/ng/journal/v39/n4/full/ng0407-423.html) to overcome these, with the focus on Mendelian disease. A considerable number of projects have been added, to those that have been ongoing for a number of years, since that meeting. Also, a planning meeting is to be held May 25-29, 2008 in Spain (http://www.humanvariomeproject.org/HVP2008/).&#xd;&#xa;&#xd;&#xa;A dramatic boost has been given to the HVP by the preparedness and action of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT; www.insight-group.org), to, in order to improve their own informatics systems for dealing with inherited colon cancer, set up a pilot system for collection and databasing mutation and phenotype information, i.e. to act as pilot for the HVP. This is then intended to be transferred to other genes and countries. Much relevant activity in this project is being led from and is based in Melbourne.&#xd;&#xa;&#xd;&#xa;This meeting in Melbourne has been conceived to review the current local situation and plans for the future. We are privileged that Myles Axton, Editor of Nature Genetics, a strong supporter of the HVP (see April 2007 Nature Genetics Editorial) and who has some ideas in the area (see August 2007 Nature Genetics Editorial) agreed to be keynote speaker.&#xd;&#xa;&#xd;&#xa;We proposed that the output of this meeting be published and, with permission, the abstracts and presentations placed on the website (www.humanvariomeproject.org/?p=Melbourne_Meeting). We also hope it will inform the May HVP Planning Meeting

GJB2 mutations and degree of hearing loss: a multicenter study.

Contains fulltext : 47828.pdf (publisher's version ) (Closed access)Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes