1) Real exome sequencing dataset on idiopathic hemolytic anemia (MIM: 266200)
We used the exome of an individual having idiopathic hemolytic anemia (IHA) for which PKLR was identified as the most likely cause of IHA(33).
| Idiopathic Hemolytic Anemia (IHA) | Input |
| 28,644 biallelic variants were ranked reporting PKLR as the 4th rank | Output |
| Applying the autosomal rare recessive model using the Result Explorer module, the number of variants reduced to 28 variants with PKLR as the top candidate gene (out of 14 candidate genes). | Output |
| Reference paper: Exome sequencing and unrelated findings in the context of complex disease research: ethical and clinical implications. | Pubmed |
1. Paste job id (nonregistered-2016-01-13_13:24:42) in check status . Submit & View full results. 2. Paste job id in Result Explorer Advanced query & select rare autosomal recessive model and press Go. 2) Synthetic whole-genome sequencing dataset on Pfeiffer syndrome (MIM: 101600)
We supplemented the p.E173A mutation in the FGFR2 gene associated with Pfeiffer syndrome (MIM:101600) into a normal exome VCF file containing 33,862 variants.
| Pfeiffer syndrome | Input |
| 33,862 variants biallelic variants were ranked reporting FGFR2 as the top candidate by rank.score | Output |
| Applying the autosomal rare dominant model using the Result Explorer module, the number of variants reduced to 541 variants with with FGFR2 still being the top candidate gene. | Output |
We supplemented two variants (p.G152R and p.G202A) in DHODH known to cause Miller syndrome ([MIM: 263750]) in the normal exome and applied the rare recessive autosomal disease model filter.
| Miller syndrome | Input |
| 33,860 variants biallelic variants were ranked | Output |
| Applying the autosomal rare recessive model using the Result Explorer module, the number of variants reduced to 59 variants (28 candidate genes), including the causal gene DHODH ranked as the top candidate gene. | Output |
Related publications:
In addition to real and synthetic validation datasets, we have applied our algorithm to targetted-resequencing data and family-exome sequencing data.
- Alexander J, Potamianou H, Xing J, Deng L, Karagiannidis I, Tsetsos F, Drineas P, Zsanett T, Rizzo R, Wolanczyk T, Farkas L, Nag y P, Szymanska U, Androutsos C, Tsironi V, Koumoula A, Barta C, Sandor P, Barr C, Tischfield J, Paschou P, Heiman G, Georgitsi M.(2016). Targeted re-sequencing approach of candidate genes implicates rare potentially functional variants in Tourette Syndrome etiology. Frontiers in Neuroscience.
- Alexander, J., Kalev, O., Mehrabian, S., Traykov, L., Raycheva, M., Kanakis, D., et al. (2016). Familial early-onset dementia with complex neuropathological phenotyp e and genomic background. Neurobiol. Aging.