Diagnostic interpretation of array data using public databases and internet sources

Abstract

The range of commercially available array platforms and analysis software packages is expanding and their utility is improving, making reliable detection of copy-number variants (CNVs) relatively straightforward. Reliable interpretation of CNV data, however, is often difficult and requires expertise. With our knowledge of the human genome growing rapidly, applications for array testing continuously broadening, and the resolution of CNV detection increasing, this leads to great complexity in interpreting what can be daunting data. Correct CNV interpretation and optimal use of the genotype information provided by single-nucleotide polymorphism probes on an array depends largely on knowledge present in various resources. In addition to the availability of host laboratories’ own datasets and national registries, there are several public databases and Internet resources with genotype and phenotype information that can be used for array data interpretation. With so many resources now available, it is important to know which are fit-for-purpose in a diagnostic setting. We summarize the characteristics of the most commonly used Internet databases and resources, and propose a general data interpretation strategy that can be used for comparative hybridization, comparative intensity, and genotype-based array data.

Upregulation of NEK2 is associated with drug resistance in ovarian cancer

“…Thus, it is fast enough to predict gene functions with great accuracy using this software. COREMINE Medical is a product of the PubGene Company designed to be used for searching information on health, medicine and biology (25). COREMINE Medical grew out of Pubgene online tool which is a gene/protein database and a web-based tool for literature mining.…”

A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors

“…The published recommendations and guidelines for classification and interpretation of CNVs for constitutional postnatal genetic diagnosis, including VOUS, form the basis for our CNV classification in the prenatal setting also. 8,[14][15][16] CNVs without genes or known to be common in the population are considered benign. A list of common polymorphic CNVs is curated by the laboratory based on in-house data and previous experience, supported by additional evidence from the database of genomic variants, DECIPHER, and ISCA databases (see Supplementary Table S2 online).…”

The introduction of arrays in prenatal diagnosis: A special challenge

“…Helpful tools to interpret CNVs are provided by several public databases that collect data from healthy subjects, such as the Database of Genomic Variants (http://projects.tcag.ca/ variation), or from patients with multiple congenital anomalies and/or developmental disabilities, such as DECIPHER (http:// decipher.sanger.ac.uk/), ECARUCA (http://www.ECARUCA.net), and ISCA (https://www.iscaconsortium.org) [de Leeuw et al, 2012]. In the near future, the growing amount of data collected by such resources will allow a much better correlation between a certain CNV and a possible pathogenic condition.…”