Human gain-of-function (GOF) and loss-of-function (LOF) pathogenic variants: a resource of all currently known human GOF and LOF germline variants, and their associated discriminative features.
- Link to webserver for extracting specific GOF/LOF variants and downloading the full database: https://itanlab.shinyapps.io/goflof/
- Link to publication: https://www.sciencedirect.com/science/article/abs/pii/S0002929721003840?dgcid=coauthor
Network-based heterogeneity clustering (NHC): a method complementary to traditional gene-burden and association case-control analysis, where disease-causing genes are identified by clustering based on biological relatedness. This approach is also highly effective in small and medium cohorts of tens of patients or more.
- Link to NHC files and documentation: https://github.com/casanova-lab/NHC
A blacklist of non-pathogenic variants: a pre-calculated list of variants that are common in exomes of patients but absent from public databases, including a software to generate in-house blacklists from patients’ NGS cohorts. Removing blacklist variants from NGS analyses filters out a median of 62% of non-pathogenic variants in patients, with very low false negative rates.
- Link to blacklist server (http://pec630.rockefeller.edu:8080/BL/)
- Link to blacklist publication (https://www.pnas.org/content/116/3/950)
Visualizing population genetics (PopViz): visualizing genetic variants in genes of interest by damage prediction scores, allele frequencies, and by specific populations.
- Link to PopViz webpage (http://shiva.rockefeller.edu/PopViz/)
- Link to PopViz publication (https://academic.oup.com/bioinformatics/article/34/24/4307/5047756)
Easy online extraction of DNA and protein sequences from NGS VCF files (SeqTailor) and by genomic coordinates.
- Link to SeqTailor webserver (http://shiva.rockefeller.edu/SeqTailor/)
- Link to SeqTailor manuscript (https://www.biorxiv.org/content/10.1101/408625v1)
Other software:
- Gene damage index (GDI): remove gene that are highly mutated in healthy individuals. http://pec630.rockefeller.edu:8080/GDI/
- Mutation significance cutoff (MSC): gene-specific cutoff scores for damage prediction scores. http://pec630.rockefeller.edu:8080/MSC/ Download updated MSC based on CADD v1.6 for 99%CI, 95%CI, and 90%CI: https://itanlab.org/wp-content/uploads/2020/06/MSC_v1.6.zip
- Human gene connectome (HGC): prioritizing candidate genes by biological distance to known disease-causing genes. http://hgc.rockefeller.edu/
Download updated HGC based on STRING v11.0: https://drive.google.com/drive/folders/1s11PH0pjIZa5R5l3Nn86rbAKZHaCSd77?usp=sharing - Closest disease genes (CDG): pre-calculated novel disease-causing genes for diseases of interest, and predicting associated diseases for novel genes. http://pec630.rockefeller.edu:8080/CDG/