AUTOMATIC ANALYSIS

AUTOMATIC ANALYSIS

Biotechnology
  • Gizem Özbek
  • August 10th 2021

NGS Cloud is a clinical decision support system that automatically presents a list of candidate variants in the light of submitted phenotypic data, with minimal or no need for filtering to reach a clinical diagnosis. The most fundamental component of this system is the GENIUS algorithm, which performs gene-genotype-phenotype matching and variant prioritisation.

 

GENIUS (GENe Interactions Under Scope)

Approximately 70,000 variants in whole-exome sequencing (WES) and 5,000,000 variants are called in whole-genome sequencing (WGS) (1). These variants are then filtered and excluded according to several different parameters, such as

  • the observed allele frequency in population-based studies, 
  • the prevalence of the disorder, 
  • the phenotypic relationship(s) of the gene, 
  • the overlapping degree of the phenotype with the samples’ phenotype, 
  • the known inheritance pattern and the compatibility of the genotype, 
  • the functional evidence in the literature, 
  • the familial segregation status, 
  • whether it has been detected in similarly affected individuals, 
  • computational & predictive effects on the protein.

 

Here, the GENIUS algorithm has been developed to automatically apply all known relevant criteria and enables you to reach the disease-causing variant faster and easier.

Inputs of the GENIUS algorithm:

 

  1. Human Phenotype Ontology (HPO) terms describing human diseases with a standard vocabulary
  2. HOPE (Harmonization of Ontologies by PairEnd) terms enriched with several different ontologies.
  3. Current age and age of onset
  4. Sex



 

In a recent validation study, GENIUS has presented six variants during a WES analysis on average (Figure 1) (2).



Figure 1. Automatically listed candidate variant numbers

 

The GENIUS algorithm listed clinically relevant variants in 94.4% of the cases. These variants were either the first or among the top three in 44.1% and 73.5% of the samples, respectively2. The GENIUS algorithm enables a straightforward analysis through tens of thousands, millions of genetic variants and identify genetic changes that cause disease, usually one or two. Most importantly, it becomes more accurate by reducing human-induced errors.

 

References:

  1. Alfares, A., Alsubaie, L., Aloraini, T., Alaskar, A., Althagafi, A., Alahmad, A., Rashid, M., Alswaid, A., Alothaim, A., Eyaid, W., Ababneh, F., Albalwi, M., Alotaibi, R., Almutairi, M., Altharawi, N., Alsamer, A., Abdelhakim, M., Kafkas, S., Mineta, K., Cheung, N., … Alfadhel, M. (2020). What is the right sequencing approach? Solo VS extended family analysis in consanguineous populations. BMC medical genomics, 13(1), 103. https://doi.org/10.1186/s12920-020-00743-8
  2. http://www.medicaljournal.gazi.edu.tr/index.php/GMJ/article/view/2914
Related Post :
Gizem Özbek August 11th 2021
Gizem Özbek August 12th 2021
Gizem Özbek August 12th 2021