**If you use FROG fingerprints or this framework for your research, please cite us as
Abinaya E, Narang P, Bhardwaj A (2015) FROG - Fingerprinting Genomic Variation Ontology.
PLoS ONE 10(8): e0134693. doi:10.1371/journal.pone.0134693
Some of the major features of FROG are:
- Organism independent.
- Developed with simpler sub-levels vocabularies which can be combined to propose a complex variation effect.
- Sub-levels are placed to include modifications in future, if required.
- Integration of tools like SIFT and POLYPHEN so that the outcome of structural changes can be associated to pathogenicity.
- Genomic variations properties are converted into fingerprints (binary codes) to make it scalable in terms of computationally storage and search.
- 1. Chromosome (13 bits)
- 1.1. Variation kind (2 bits)
- 1.1.1. Indel (01)
- 1.1.2. Insertion (10)
- 1.1.3. Deletion (11)
- 1.1.4. Substitution (00)
- 1.2. Repeats (3 bits)
- 1.2.1. Mono-nucleotide expansion Microsatellite (000)
- 1.2.2. Minisatellite (001)
- 1.2.3. Mobile elements (010)
- 1.2.4. Tandem repeats binucleotides (011)
- 1.2.5. Trinucleotide expansion (110)
- 1.2.6. Tetranucleotide expansion (111)
- 1.2.7. Interspersed Hexaploidy (101)
- 1.2.8. No amplification (100)
- 1.3. Location (1 bit)
- 1.3.1. Autosomes (0)
- 1.3.2. Allosomes (1)
- 1.4. Variation number (4 bits)
- 1.4.1. Set number (0)
- 1.4.1.1. Nulliploidy (010)
- 1.4.1.2. Monoploidy (001)
- 1.4.1.3. Diploidy (000)
- 1.4.1.4. Triploidy (011)
- 1.4.1.5. Tetraploidy (111)
- 1.4.1.6. Pentaploidy (101)
- 1.4.1.7. Hexaploidy (110)
- 1.4.1.8. Polyploidy (100)
- 1.4.2. Number (1)
- 1.4.2.1. Nullisomy (111)
- 1.4.2.2. Monosomy (011)
- 1.4.2.3. Disomy (000)
- 1.4.2.4. Iso-Disomy (001)
- 1.4.2.5. Hetero-Disomy (010)
- 1.4.2.6. Trisomy (100)
- 1.4.2.7. Tetrasomy (110)
- 1.4.2.8. Polysomy (101)
- 1.4.1. Set number (0)
- 1.5. Structural variation (3 bits)
- 1.5.1. Complex (1)
- 1.5.1.1. Uncharacterized (100)
- 1.5.1.2. Telomere changes (101)
- 1.5.1.3. Interstetial deletion (110)
- 1.5.1.4. Isochromosome (111)
- 1.5.2. Translocation (0)
- 1.5.2.1. Intra (0)
- 1.5.2.1.1. Para intra-translocation (0)
- 1.5.2.1.2. Peri intra-translocation (1)
- 1.5.2.2. Inter (1)
- 1.5.2.2.1. Reciprocal inter-translocation (0)
- 1.5.2.2.2. Robert inter-translocation (1)
- 1.5.2.1. Intra (0)
- 1.5.1. Complex (1)
- 1.1. Variation kind (2 bits)
- 2. DNA (15 bits)
- 2.1. Variation kind (3 bits)
- 2.1.1. Indel (000)
- 2.1.2. Insertion (011)
- 2.1.3. Deletion (001)
- 2.1.4. Translocation (111)
- 2.1.5. Inversion (110)
- 2.1.6. Transition (010)
- 2.1.7. Transversion (100)
- 2.1.8. No defined change (101)
- 2.2. Transition type (2 bits)
- 2.2.1. A to G purine transition (00)
- 2.2.2. G to A purine transition (01)
- 2.2.3. C to T pyrimidine transition (10)
- 2.2.4. T to C pyrimidine transition (11)
- 2.3. Transversion type (3 bits)
- 2.3.1. A to C transversion (100)
- 2.3.2. A to T transversion (001)
- 2.3.3. G to C transversion (011)
- 2.3.4. G to T transversion (010)
- 2.3.5. C to A transversion (000)
- 2.3.6. C to G transversion (111)
- 2.3.7. T to A transversion (101)
- 2.3.8. T to G transversion (110)
- 2.4. Epigenetic variations (1 bit)
- 2.4.1. DNA methylation(1)
- 2.4.2. DNA remodelling (0 )
- 2.5. Gene fusion (1 bit)
- 2.5.1. Gene fusion occured (1)
- 2.5.2. Gene fusion not occured (0)
- 2.6. Structural variation (3 bits)
- 2.6.1. Secondary structure (1)
- 2.6.1.1. DNA G-quadruplex (00)
- 2.6.1.2. I motif (01)
- 2.6.1.3. Triple stranded (11)
- 2.6.1.4. DNA stem (10)
- 2.6.2. Level affected (0)
- 2.6.2.1. Intron (00)
- 2.6.2.2. Exon (01)
- 2.6.2.3. Extra DNA (11)
- 2.6.2.4. Chromatin (10)
- 2.6.1. Secondary structure (1)
- 2.7. Function Level (2 bits)
- 2.7.1. DNA replication (00)
- 2.7.2. DNA repair (01)
- 2.7.3. Effect on promoter activity- REG function of DNA (10)
- 2.7.4. Effect on transcription (11)
- 2.1. Variation kind (3 bits)
- 3. RNA (23 bits)
- 3.1. Variation kind (3 bits)
- 3.1.1. Indel (000)
- 3.1.2. Insertion (011)
- 3.1.3. Deletion (001)
- 3.1.4. Translocation (111)
- 3.1.5. Inversion (110)
- 3.1.6. Transition (010)
- 3.1.7. Transversion (100)
- 3.1.8. No defined change (101)
- 3.2. Transition type (2 bits)
- 3.2.1. A to G purine transition (00)
- 3.2.2. G to A purine transition (01)
- 3.2.3. C to U pyrimidine transition (10)
- 3.2.4. U to C pyrimidine transition (11)
- 3.3. Transversion type (3 bits)
- 3.3.1. A to C transversion (100)
- 3.3.2. A to U transversion (001)
- 3.3.3. G to C transversion (011)
- 3.3.4. G to U transversion (010)
- 3.3.5. C to A transversion (000)
- 3.3.6. C to G transiversion (111)
- 3.3.7. U to A transversion (101)
- 3.3.8. U to G transversion (110)
- 3.4. Splicing (3 bits)
- 3.4.1. Cis splicing (1)
- 3.4.1.1. Place (1)
- 3.4.1.1.1. 3-prime(1)
- 3.4.1.1.2. 5-prime (0)
- 3.4.1.2. Type (0)
- 3.4.1.2.1. Canonical(1)
- 3.4.1.2.2. Non-canonical (0)
- 3.4.1.1. Place (1)
- 3.4.2. Other kinds(0)
- 3.4.2.1. Acceptor-new site generation (00)
- 3.4.2.2. Donor-new site generation (01)
- 3.4.2.3. No trans splicing (11)
- 3.4.2.4. Trans Splicing (10)
- 3.4.1. Cis splicing (1)
- 3.5. Property changes (3 bits)
- 3.5.1. No effect (000)
- 3.5.2. Nonsense (110)
- 3.5.3. Nonstop (101)
- 3.5.4. RNA abundance (100)
- 3.5.5. RNA folding (011)
- 3.5.6. RNA Interaction (010)
- 3.5.7. RNA stability (001)
- 3.5.8. Non-GO (111)
- 3.6. Secondary structure changes (3 bits)
- 3.6.1. Loop (1)
- 3.6.1.1. Hairpin (00)
- 3.6.1.2. Interior Loop,multi loop (01)
- 3.6.1.3. Multiloop (11)
- 3.6.1.4. Uncharacterised Loop (10)
- 3.6.2. Others (0)
- 3.6.2.1. Bulge (00)
- 3.6.2.2. No effect on secondary structure (11)
- 3.6.2.3. Pseudoknots (10)
- 3.6.2.4. Stem (01)
- 3.6.1. Loop (1)
- 3.7. Affected Level (3 bits)
- 3.7.1. Composition (00)
- 3.7.1.1. Nucleoside (0)
- 3.7.1.2. Base (1)
- 3.7.2. Frame changes (11)
- 3.7.2.1. Outframe (0)
- 3.7.2.2. Inframe (1)
- 3.7.3. Coding (01)
- 3.7.3.1. Exons (0)
- 3.7.3.2. Introns (1)
- 3.7.4. Non-genetic (10)
- 3.7.4.1. decayed-RNA (0)
- 3.7.4.2. modified RNA (1)
- 3.7.1. Composition (00)
- 3.8. Mechanism changes (1 bit)
- 3.8.1. Silent (1)
- 3.8.2. Non-sense (0)
- 3.9. Functional changes (2 bits)
- 3.9.1. Effect on RNA information transfer (00)
- 3.9.2. Effect on translation (01)
- 3.9.3. Effect on regulatory activity (10)
- 3.9.4. Effect on amino acid transfer function of RNA (11)
- 3.1. Variation kind (3 bits)
- 4. Protein (22 bits)
- 4.1. Variation kind (2 bits)
- 4.1.1. Indel (01)
- 4.1.2. Insertion (10)
- 4.1.3. Deletion (11)
- 4.1.4. Substitution (00)
- 4.2. Accessibility (1 bit)
- 4.2.1. Buried (1)
- 4.2.2. Exposed (0)
- 4.3. Predicted pathogenecity (4 bits)
- 4.3.1. Sift and Polyphen(1)
- 4.3.1.1. unknown(p)+tolerated(s) (000)
- 4.3.1.2. probably Damaging(p)+damaging(s) (001)
- 4.3.1.3. possibly Damaging(p)+tolerated(s) (010)
- 4.3.1.4. probably damaging(p)+tolerated(s) (011)
- 4.3.1.5. unknown(p)+damaging(s) (100)
- 4.3.1.6. benign(p)+tolerated(s) (101)
- 4.3.1.7. possibly Damaging(p)+damaging(s) (110)
- 4.3.1.8. benign(p)+damaged(s) (111)
- 4.3.2. Either of the above (0)
- 4.3.2.1. Sift (1)
- 4.3.2.1.1. Tolerated(01)
- 4.3.2.1.2. Damaging (10)
- 4.3.2.1.3. Unknown (00)
- 4.3.2.1.4. Tolerated low confidence (11)
- 4.3.2.2. Polyphen (0)
- 4.3.2.2.1. Possible damaging (00)
- 4.3.2.2.2. Probably damaging (01)
- 4.3.2.2.3. Unknown (10)
- 4.3.2.2.4. Benign (11)
- 4.3.2.1. Sift (1)
- 4.3.1. Sift and Polyphen(1)
- 4.4. Protein dynamics (2 bits)
- 4.4.1. Effect on allosteric site (00)
- 4.4.2. Effect on induced site (01)
- 4.4.3. Effect on structure disorder (11)
- 4.4.4. Effect on structure flexibility (10)
- 4.5. Property variation (3 bits)
- 4.5.1. Effect on protein sub cellular localization (000)
- 4.5.2. Effect on protein accessibility (001)
- 4.5.3. Effect on protein abundance (010)
- 4.5.4. Effect on protein electrostatics (011)
- 4.5.5. Effect on protein degradation (100)
- 4.5.6. Effect on protein aggregation (101)
- 4.5.7. Effect on protein activity (110)
- 4.5.8. Effect on protein precipitation (111)
- 4.6. Structural variation (5 bits)
- 4.6.1. Secondary structure (1)
- 4.6.1.1. Helix (01)
- 4.6.1.1.1. Effect on left handed protein helix (00)
- 4.6.1.1.2. Effect on alpha helix (01)
- 4.6.1.1.3. Effect on Pi helix (10)
- 4.6.1.1.4. Effect on three ten helix (11)
- 4.6.1.2. Effect on turns (10)
- 4.6.1.2.1. Effect on ASX turn (00)
- 4.6.1.2.2. Effect on ST turn (01)
- 4.6.1.2.3. Effect on protein beta turn (10)
- 4.6.1.2.4. Effect on protein gamma turn (11)
- 4.6.1.3. Beta/Loop (11)
- 4.6.1.3.1. Beta (0)
- 4.6.1.3.1.1. Parallel (0)
- 4.6.1.3.1.2. Anti-parallel (1)
- 4.6.1.3.2. Effect on Loops (1)
- 4.6.1.3.2.1. Effect on protein schellman loop (0)
- 4.6.1.3.2.2. Effect on protein beta bulge loop (1)
- 4.6.1.3.1. Beta (0)
- 4.6.1.4. Others (00)
- 4.6.1.4.1. Effect on beta bulge (00)
- 4.6.1.4.2. Coil (10)
- 4.6.1.4.3. Effect on ST staple (11)
- 4.6.1.4.4. Unknown (01)
- 4.6.1.1. Helix (01)
- 4.6.2. Tertiary structure (0)
- 4.6.2.1. Local protein conformation change (0000)
- 4.6.2.2. Global protein conformation change (0001)
- 4.6.2.3. protein overpacking (0101)
- 4.6.2.4. Effect on folding rate (0010)
- 4.6.2.5. Changed domain orientation (0011)
- 4.6.2.6. N-terminal protein elongation (0100)
- 4.6.2.7. Generation of a novel post translational modification (0101)
- 4.6.2.8. Effect on intra transmembrane polypeptide (0110)
- 4.6.2.9. variation preventing polypeptide processing (0111)
- 4.6.2.10. protein cavity formation (1000)
- 4.6.2.11. C-terminal protein elongation (1001)
- 4.6.2.12. Effect on extra transmembrane polypeptide (1010)
- 4.6.2.13. Protein truncation change (1011)
- 4.6.2.14. Deletion of a post translational modification site (1100)
- 4.6.2.15. Protein fusion - protein elongation (1101)
- 4.6.2.16. Effect on protein splicing (1111)
- 4.6.1. Secondary structure (1)
- 4.7. Functional variation (3 bits)
- 4.7.1. Effect on protein storage (000)
- 4.7.2. Neomorphic protein variation (001)
- 4.7.3. Effect on protein information transfer (010)
- 4.7.4. Effect on protein movement (011)
- 4.7.5. Antimorphic protein variation (100)
- 4.7.6. Effect on transport function of protein (101)
- 4.7.7. Loss of function (110)
- 4.7.8. Epigenetic changes (111)
- 4.8. Effect on motif (2 bits)
- 4.8.1. Effect on protein niche motif (00)
- 4.8.2. Effect on protein ASX motif (01)
- 4.8.3. Effect on protein NEST motif (10)
- 4.8.4. Effect on protein ST motif (11)
- 4.1. Variation kind (2 bits)
- 5. Variations (18 bits)
- 5.1. Variation origin (2 bits)
- 5.1.1. Non-genetic origin (10)
- 5.1.2. Paternal (00)
- 5.1.3. Maternal (01)
- 5.1.4. Both (11)
- 5.2. Variation size (1 bit)
- 5.2.1. Streched (1)
- 5.2.2. Single nucleotide (0)
- 5.3. Variation type (1 bit)
- 5.3.1. Synonymous (1)
- 5.3.2. Non-synonymous (0)
- 5.4. Experimental classification (1 bit)
- 5.4.1. Tissue details available (1)
- 5.4.2. Tissue details not available (0)
- 5.5. Details (1 bit)
- 5.5.1. Experimental data available (1)
- 5.5.2. Experimental data not available (0)
- 5.6. Geographical details (2 bits)
- 5.6.1. Yoruba in Ibadan, Nigeria (YRI) (00)
- 5.6.2. Japanese in Tokyo, Japan (JPT) (11)
- 5.6.3. Han Chinese in Beijing, China (CHB) (01)
- 5.6.4. CEPH (Utah residents with ancestry from northern and western Europe) (10)
- 5.7. Pathogenecity (2 bits)
- 5.7.1. Repeats disease associated pathogenecity association (00)
- 5.7.2. Disease causing pathogenecity association (01)
- 5.7.3. Associated variants disease associated pathogenecitty association (10)
- 5.7.4. Not related to clinical phenotype pathogenecitty association (11)
- 5.8. MAF data (1 bit)
- 5.8.1. Greater than 1% (1)
- 5.8.2. Less than 1% (0)
- 5.9. CPV data (1 bit)
- 5.9.1. Reported (1)
- 5.9.2. Not reported (0)
- 5.10. Conservation (1 bit)
- 5.10.1. Variant (0)
- 5.10.2. Invariant (1)
- 5.11. Mesh term (1 bit)
- 5.11.1. Available (1) 1i>
- 5.11.2. Not Available (0)
- 5.12. D.rerio (1 bit)
- 5.12.1. Reported as model (1)
- 5.12.2. Not reported (0)
- 5.13. Mus musculus (1 bit)
- 5.13.1. Reported as model (1)
- 5.13.2. Not reported (0)
- 5.14. D.melangoster (1 bit)
- 5.14.1. Reported as model (1)
- 5.14.2. Not reported (0)
- 5.15. C.elegans (1 bit)
- 5.15.1. Reported as model (1)
- 5.15.2. Not reported (0)
- 5.1. Variation origin (2 bits)
- 6. Interactions (11 bits)
- 6.1. Complex type (2 bits)
- 6.1.1. Protein-DNA complex (11)
- 6.1.2. Protein-protein complex (10)
- 6.1.3. Riboprotein complex (00)
- 6.1.4. Protein-small molecule complex (01)
- 6.2.Genetic Interaction (4 bits)
- 6.2.1. Double non-monotonic genetic interaction defined by inequality (0000)
- 6.2.2. Non-interactive genetic variation defined by inequality- Neutral genetic interaction (0001)
- 6.2.3. Additive genetic interaction defined by inequality (1110)
- 6.2.4. Conditional genetic interaction defined by inequality (0100)
- 6.2.5. Asynthetic genetic interaction defined by inequality (0110)
- 6.2.6. Single non-monotonic genetic interaction defined by inequality (0111)
- 6.2.7. Colocalization (0101)
- 6.2.8. Suppressive genetic variation defined by inequality - Epistatic genetic interaction (1111)
- 6.2.9. Association (1100)
- 6.2.10. Epistatic genetic variation defined by inequality - Epistatic genetic interaction (1101)
- 6.2.11. Synthetic genetic variation defined by inequality - Negative interaction (1011)
- 6.2.12. Inequality (1010)
- 6.2.13. Negative interaction (1000)
- 6.2.14. Neutral interaction (0011)
- 6.2.15. Not defined (1001)
- 6.2.16. Positive interaction (0010)
- 6.3. Bonds (3 bits)
- 6.3.1. Common (00)
- 6.3.1.1. Disulphide bridge-covalent bond (0)
- 6.3.1.2. Hydrogen bond network (1)
- 6.3.2. Structural (01)
- 6.3.2.1. Inter-molecular (0)
- 6.3.2.2. Intra-molecular (1)
- 6.3.3. Other (10)
- 6.3.3.1. Vander waals interactions (0)
- 6.3.3.2. Hydrophobic interaction (1)
- 6.3.4. Charged (11)
- 6.3.4.1. Salt bridge-non covalent bond (0)
- 6.3.4.2. Electrostatic interaction non-covalent bond (1)
- 6.3.1. Common (00)
- 6.4. Interactors (2 bits)
- 6.4.1. Biopolymer (0)
- 6.4.1.1. Polysachharide (0)
- 6.4.1.2. Peptide (1)
- 6.4.2. Small molecule (1)
- 6.4.2.1. Metal (0)
- 6.4.2.2. Water (1)
- 6.4.1. Biopolymer (0)
- 6.1. Complex type (2 bits)