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Genes Fold Enrichment Color Codes
  • Gene Name, Canonical Transcript - gene identifiers from gnomAD database (Build 37)
  • GeVIR % - gene rank measured in percentiles based on Gene Variation Intolerance Ranking (GeVIR) (low values indicate more variation intolerant genes, which is also true for "LOEUF %" and "VIRLoF %"). GeVIR is a method which we developed and applied on a list of 19,361 genes to sort them based on number, length and evolutionary conservation of regions without functional variants (i.e. between two missense, loss-of-function, insertion or delition variants) in gnomAD database (version 2.0.1). Only canonical transcripts were analysed.
  • LOEUF % - gene rank measured in percentiles based gnomAD loss-of-function observed/expected upper bound fraction (LOEUF) (see Figure 1). For more information about this metric, please read "Constraint" section of MacArthur Lab blog post. If you use this metric please cite gnomAD flagship paper and use most up-to-date values from gnomAD website.

    LoF observed/expected (o/e) upper Confidence Interval (CI)

    Figure 1. Screenshot of ELN gene constraint metrics from gnomAD browser

  • VIRLoF % - gene rank measured in percentiles based on both GeVIR and gnomAD LOEUF (shows the best overall performance, see Figure 2). If you use this metric please cite both GeVIR and gnomAD flagship paper.
  • GeVIR AD, LOEUF AD, VIRLoF AD, GeVIR AR, LOEUF AR, VIRLoF AR - to help users interpret gene ranks, we calculated fold enrichment of Autosomal Dominant (AD) and Autosomal Recessive (AR) genes with known molecular basis of disorder in OMIM in a range of +-5% of gene X (see Figure 2). Statistical significant fold enrichements (Fisher Exact Test p-value < 1e-5) are shown in bold in the table. For example CDK19 gene's GeVIR % is 2.37, so examined range is from 0 (2.37-5, rounded to minimal percentile) to 7.37% (2.37+5). Genes in this range are ~4 times more often (4.05 fold enrichement) associated with AD diseases and ~4 times less often (0.25 fold enrichement) associated with AR diseases. Both enrichment of AD genes and deficiency of AR genes is statistical significant. Thus GeVIR metric adds supportive evidence that CDK19 is more likely to be associated with AD than AR disease.

    Gene Percentiles AD AR Fold Enrichment

    Figure 2. Fold Enrichment of known Autosomal Dominant (AD) and Autosomal Recessive (AR) genes of each gene in the ranked lists (GeVIR, LOEUF, VIRLoF. AD genes are enriched among top ranked genes (lowest percentiles), whereas AR genes are enriched among middle ranked genes (approximetly 35-65 percentiles). Combined metric (VIRLoF, purple) shows the best perfornance, i.e. high ranked genes are more often associated with AD than AR diseases, low ranked genes are less often associated with both AD and AR diseases.
Gene Name Canonical Transcript GeVIR % LOEUF % VIRLoF % GeVIR AD LOEUF AD VIRLoF AD GeVIR AR LOEUF AR VIRLoF AR
ZNF799 ENST00000430385 96.18 81.79 91.80 0.11 0.34 0.14 0.11 0.51 0.18
ZNF8 ENST00000196548 47.68 37.49 40.76 0.53 0.78 0.81 1.80 1.67 2.04
ZNF8 ENST00000608843 47.69 37.52 40.75 0.53 0.78 0.81 1.80 1.66 2.04
ZNF80 ENST00000482457 88.74 99.35 96.27 0.19 0.16 0.07 0.33 0.12 0.09
ZNF800 ENST00000393313 14.39 3.49 6.22 1.57 3.38 3.15 0.73 0.29 0.32
ZNF804A ENST00000302277 59.93 21.40 39.00 0.63 1.43 0.80 1.39 0.80 2.06
ZNF804B ENST00000333190 54.86 54.09 53.95 0.65 0.65 0.61 1.71 1.68 1.77
ZNF805 ENST00000414468 51.37 23.52 35.59 0.59 1.39 0.86 1.85 0.92 1.77
ZNF808 ENST00000359798 97.00 65.03 84.34 0.09 0.51 0.33 0.11 1.24 0.40
ZNF81 ENST00000376954 37.05 25.01 29.18 0.92 1.33 0.84 1.76 1.05 1.33
ZNF812 ENST00000457674 95.25 96.75 98.31 0.10 0.23 0.09 0.11 0.19 0.05
ZNF813 ENST00000396403 95.10 47.67 74.24 0.10 0.61 0.39 0.12 1.97 0.69
ZNF814 ENST00000435989 97.61 86.24 94.66 0.10 0.27 0.09 0.11 0.43 0.11
ZNF816 ENST00000357666 97.09 94.87 98.30 0.10 0.23 0.09 0.11 0.23 0.05
ZNF821 ENST00000425432 19.51 37.71 26.78 1.57 0.78 0.96 1.00 1.70 1.27
ZNF823 ENST00000341191 99.80 55.75 81.13 0.12 0.52 0.39 0.13 1.59 0.49
ZNF827 ENST00000379448 17.44 8.08 10.33 1.46 2.52 2.19 0.87 0.44 0.43
ZNF829 ENST00000520965 59.68 67.20 64.85 0.58 0.54 0.51 1.41 1.22 1.34
ZNF83 ENST00000597597 98.36 98.54 99.57 0.10 0.20 0.12 0.10 0.15 0.05
ZNF830 ENST00000361952 33.04 40.47 34.93 0.94 0.62 0.90 1.71 1.76 1.77
ZNF831 ENST00000371030 85.57 38.57 63.15 0.28 0.72 0.49 0.46 1.67 1.37
ZNF835 ENST00000537055 97.03 98.52 99.46 0.10 0.21 0.11 0.11 0.15 0.05
ZNF836 ENST00000322146 97.26 96.86 99.02 0.10 0.23 0.11 0.11 0.19 0.04
ZNF837 ENST00000427624 91.03 85.99 91.59 0.16 0.27 0.15 0.21 0.43 0.18
ZNF839 ENST00000442396 84.52 42.11 64.67 0.30 0.61 0.51 0.46 1.86 1.32

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