The Human Phenotype Ontology (HPO) was developed to provide an ontology of phenotypic anomalies that have been associated with disorders in the Online Mendelian Inheritance in Man (OMIM) database1. In a broad sense, an ontology is the philosophical discipline that studies the nature of existence and aims to understand how things in the world are divided into categories and how these categories are related together. For example, each term in the HPO is related to each other in a hierarchy.
The association of HPO terms to disorders allows potential disorders to be identified based on a patient's clinical phenotypes (Phenomizer) and can be used to prioritise genetic variants in an individual (Exomiser and Genomiser). The HPO resource has also been leveraged by others to help identify potential diseases and their associated genes (Phenolyzer).
- The Phenomizer2: match a list of HPO terms to an OMIM disease
- The Exomiser3: an ensemble of tools that can prioritise variants based on HPO terms and find new genes associated with known disease causing genes
- The Genomiser4: the Genomiser uses the Exomiser framework to analyse whole-genome data and has been especially tailored to include non-coding variants
- Phenolyzer5: free text to list of genes that are related to the input
There are several directories in this repository; below is a brief description.
- cluster - cluster analysis on OMIM phenotypes
- data - contains the data used for the scripts
- exomiser - analysis using the Exomiser
- gene - analyses using genes
- phenolyzer - analysis using Phenolyzer
- prop - analyses on the properties of HPO terms
- script - basic scripts for working with HPO terms
I have written some basic scripts in Perl and R to make use of HPO terms. The script makes use of the hp.obo.gz and phenotype_annotation.tab.gz files, which can be downloaded from the downloads page of the HPO site.
The script text_to_hpo_term.pl is used to find HPO terms that match your input text.
script/text_to_hpo_term.pl
Usage: script/text_to_hpo_term.pl <infile.txt>
# using a test file with two lines of text
cat script/input.txt
focal seizures
deep set eyes
# running the script
script/text_to_hpo_term.pl script/input.txt
focal seizures: HP:0007359
Matched 1 term/s out of a total of 2. 1 term/s could not be matched:
deep set eyes
=====================================
deep set eyes
=====================================
Best match/es for deep set eyes with a mismatch score of 1:
deep-set eyes: HP:0000490
deep set eye: HP:0000490
Best match/es for deep set eyes with a mismatch score of 2:
Best match/es for deep set eyes with a mismatch score of 3:
deeply set eye: HP:0000490There is a direct match for focal seizures to HP:0007359. The term deep set eyes is not an exact HPO term but the script finds the next best match which is deep set eye or deep-set eyes, corresponding to HP:0000490.
The script hpo_to_term.pl lists all the synonyms for a HPO ID, the depth of the HPO term, the number of OMIM disorders and genes associated with the ID.
script/hpo_to_term.pl HP:0007359
HP:0007359 level: 5 disease associations: 15 gene associations: 42
focal seizures
partial seizuresThe script hpo_to_tree.pl shows the ancestors of a HPO term.
script/hpo_to_tree.pl HP:0007359
HP:0007359 focal seizures
HP:0001250 seizures
HP:0012638 abnormality of nervous system physiology
HP:0000707 abnormality of the nervous system
HP:0000118 phenotypic abnormality
HP:0000001 all
Level 5The script hpo_to_disease.pl finds OMIM disorders associated with a HPO ID.
script/hpo_to_disease.pl HP:0007359
HP:0007359
EPILEPSY, FEMALE-RESTRICTED, WITH MENTAL RETARDATION
#300491 EPILEPSY, X-LINKED, WITH VARIABLE LEARNING DISABILITIES AND BEHAVIORDISORDERS
#300643 ROLANDIC EPILEPSY, MENTAL RETARDATION, AND SPEECH DYSPRAXIA, X-LINKED;RESDX
#600513 EPILEPSY, NOCTURNAL FRONTAL LOBE, 1; ENFL1
%601764 SEIZURES, BENIGN FAMILIAL INFANTILE, 1; BFIS1;;CONVULSIONS, BENIGN FAMILIAL INFANTILE, 1; BFIC1
MYOCLONIC EPILEPSY, INFANTILE
#607745 SEIZURES, BENIGN FAMILIAL INFANTILE, 3; BFIS3;;CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; BFIC3;;SEIZURES, BENIGN FAMILIAL NEONATAL-INFANTILE; BFNIS
#611277 GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 3; GEFSP3;;GEFS+, TYPE 3; GEFS+3FEBRILE SEIZURES, FAMILIAL, 8, INCLUDED; FEB8, INCLUDED
#613060 EPILEPSY, IDIOPATHIC GENERALIZED, SUSCEPTIBILITY TO, 10; EIG10GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 5, SUSCEPTIBILITYTO, INCLUDED; GEFS5, INCLUDED;;GEFS+, TYPE 5, SUSCEPTIBILITY TO, INCLUDED;;GEFS+5, SUSCEPTIBILITY TO, INCLUDED;;GEFSP5, SUSCEPTIBILITY TO, INCLUDED;;EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 7, INCLUDED; EJM7,INCLUDED
%613608 EPILEPSY, FAMILIAL ADULT MYOCLONIC, 3; FAME3;;CORTICAL MYOCLONIC TREMOR WITH EPILEPSY, FAMILIAL, 3; FCMTE3
#613722 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 12; EIEE12
#613863 GENERALIZED EPILEPSY WITH FEBRILE SEIZURES PLUS, TYPE 7; GEFSP7;;GEFS+, TYPE 7; GEFS+7FEBRILE SEIZURES, FAMILIAL, 3B, INCLUDED; FEB3B, INCLUDED
#614563 MENTAL RETARDATION, AUTOSOMAL DOMINANT 13; MRD13;;MENTAL RETARDATION, AUTOSOMAL DOMINANT, 13, WITH NEURONAL MIGRATIONDEFECTS
#615005 EPILEPSY, NOCTURNAL FRONTAL LOBE, 5; ENFL5
#615476 EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 18; EIEE18
HP:0007359 15The script omim_to_hpo.pl finds HPO IDs associated with an OMIM disorder ID and in addition, lists the number of disease and gene associations for each HPO term. This gives you an indication of how specific a HPO term is.
script/omim_to_hpo.pl 147920
OMIM:147920 #147920 KABUKI SYNDROME 1; KABUK1;;KABUKI SYNDROME;;KABUKI MAKE-UP SYNDROME; KMS;;NIIKAWA-KUROKI SYNDROME
HP:0000006 autosomal dominant inheritance no. disease association: 2675 no. gene association: 1238
HP:0000028 cryptorchidism no. disease association: 593 no. gene association: 455
HP:0000054 micropenis no. disease association: 139 no. gene association: 137
HP:0000074 ureteropelvic junction obstruction no. disease association: 10 no. gene association: 13
HP:0000164 abnormality of the teeth no. disease association: 159 no. gene association: 561
HP:0000175 cleft palate no. disease association: 586 no. gene association: 352
HP:0000218 high palate no. disease association: 313 no. gene association: 340
HP:0000252 microcephaly no. disease association: 959 no. gene association: 624
HP:0000358 posteriorly rotated ears no. disease association: 127 no. gene association: 238
HP:0000365 hearing impairment no. disease association: 483 no. gene association: 888
HP:0000400 macrotia no. disease association: 190 no. gene association: 122
HP:0000403 recurrent otitis media no. disease association: 54 no. gene association: 56
HP:0000431 wide nasal bridge no. disease association: 298 no. gene association: 317
HP:0000437 depressed nasal tip no. disease association: 12 no. gene association: 17
HP:0000486 strabismus no. disease association: 581 no. gene association: 521
HP:0000508 ptosis no. disease association: 489 no. gene association: 397
HP:0000535 sparse eyebrow no. disease association: 70 no. gene association: 62
HP:0000592 blue sclerae no. disease association: 89 no. gene association: 57
HP:0000637 long palpebral fissure no. disease association: 32 no. gene association: 20
HP:0000851 congenital hypothyroidism no. disease association: 14 no. gene association: 15
HP:0000957 cafe-au-lait spot no. disease association: 79 no. gene association: 81
HP:0001007 hirsutism no. disease association: 64 no. gene association: 138
HP:0001212 prominent fingertip pads no. disease association: 9 no. gene association: 7
HP:0001249 intellectual disability no. disease association: 971 no. gene association: 1114
HP:0001250 seizures no. disease association: 1295 no. gene association: 1019
HP:0001252 muscular hypotonia no. disease association: 1014 no. gene association: 943
HP:0001263 global developmental delay no. disease association: 734 no. gene association: 911
HP:0001374 congenital hip dislocation no. disease association: 41 no. gene association: 47
HP:0001382 joint hypermobility no. disease association: 234 no. gene association: 199
HP:0001629 ventricular septal defect no. disease association: 304 no. gene association: 206
HP:0001631 atria septal defect no. disease association: 244 no. gene association: 205
HP:0001680 coarctation of aorta no. disease association: 42 no. gene association: 47
HP:0001878 hemolytic anemia no. disease association: 73 no. gene association: 84
HP:0001973 autoimmune thrombocytopenia no. disease association: 14 no. gene association: 24
HP:0002023 anal atresia no. disease association: 68 no. gene association: 105
HP:0002024 malabsorption no. disease association: 147 no. gene association: 172
HP:0002025 anal stenosis no. disease association: 18 no. gene association: 25
HP:0002100 recurrent aspiration pneumonia no. disease association: 6 no. gene association: 4
HP:0002553 highly arched eyebrow no. disease association: 96 no. gene association: 82
HP:0002566 intestinal malrotation no. disease association: 92 no. gene association: 66
HP:0002650 scoliosis no. disease association: 746 no. gene association: 567
HP:0003468 abnormality of the vertebrae no. disease association: 20 no. gene association: 291
HP:0004322 short stature no. disease association: 1351 no. gene association: 811
HP:0004467 preauricular pit no. disease association: 34 no. gene association: 37
HP:0004736 crossed fused renal ectopia no. disease association: 2 no. gene association: 5
HP:0005218 anoperineal fistula no. disease association: 1 no. gene association: 2
HP:0007655 eversion of lateral third of lower eyelids no. disease association: 2 no. gene association: 4
HP:0008872 feeding difficulties in infancy no. disease association: 240 no. gene association: 287
HP:0008897 postnatal growth retardation no. disease association: 87 no. gene association: 101
HP:0009237 short 5th finger no. disease association: 15 no. gene association: 25
HP:0010314 premature thelarche no. disease association: 3 no. gene association: 5
51 HPO terms
HP:0000006;HP:0000028;HP:0000054;HP:0000074;HP:0000164;HP:0000175;HP:0000218;HP:0000252;HP:0000358;HP:0000365;HP:0000400;HP:0000403;HP:0000431;HP:0000437;HP:0000486;HP:0000508;HP:0000535;HP:0000592;HP:0000637;HP:0000851;HP:0000957;HP:0001007;HP:0001212;HP:0001249;HP:0001250;HP:0001252;HP:0001263;HP:0001374;HP:0001382;HP:0001629;HP:0001631;HP:0001680;HP:0001878;HP:0001973;HP:0002023;HP:0002024;HP:0002025;HP:0002100;HP:0002553;HP:0002566;HP:0002650;HP:0003468;HP:0004322;HP:0004467;HP:0004736;HP:0005218;HP:0007655;HP:0008872;HP:0008897;HP:0009237;HP:0010314;
---------------------------
# anoperineal fistula is only associated to one disorder
script/hpo_to_disease.pl HP:0005218
HP:0005218
147920 #147920 KABUKI SYNDROME 1; KABUK1;;KABUKI SYNDROME;;KABUKI MAKE-UP SYNDROME; KMS;;NIIKAWA-KUROKI SYNDROME
HP:0005218 1
# HP:0010314 premature thelarche no. disease association: 3 no. gene association: 5
script/hpo_to_disease.pl HP:0010314
HP:0010314
147920 #147920 KABUKI SYNDROME 1; KABUK1;;KABUKI SYNDROME;;KABUKI MAKE-UP SYNDROME; KMS;;NIIKAWA-KUROKI SYNDROME
180849 #180849 RUBINSTEIN-TAYBI SYNDROME 1; RSTS1;;RUBINSTEIN SYNDROME;;BROAD THUMBS AND GREAT TOES, CHARACTERISTIC FACIES, AND MENTAL RETARDATION;;BROAD THUMB-HALLUX SYNDROME
615346 #615346 PRECOCIOUS PUBERTY, CENTRAL, 2; CPPB2
HP:0010314 3- The Human Phenotype Ontology: a tool for annotating and analyzing human hereditary disease
- Clinical diagnostics in human genetics with semantic similarity searches in ontologies.
- Next-generation diagnostics and disease-gene discovery with the Exomiser
- A Whole-Genome Analysis Framework for Effective Identification of Pathogenic Regulatory Variants in Mendelian Disease
- Phenolyzer: phenotype-based prioritization of candidate genes for human diseases