diff --git a/docs/report/tbx5_frameshift_vs_missense.csv b/docs/report/tbx5_frameshift_vs_missense.csv index e4a80ba21..421e69272 100644 --- a/docs/report/tbx5_frameshift_vs_missense.csv +++ b/docs/report/tbx5_frameshift_vs_missense.csv @@ -14,19 +14,21 @@ Pulmonary arterial hypertension [HP:0002092],4/6,67%,0/2,0%,0.6233766233766234,0 Hypoplasia of the ulna [HP:0003022],1/12,8%,2/10,20%,0.7619047619047618,0.5714285714285713 Hypoplasia of the radius [HP:0002984],30/62,48%,6/14,43%,0.9520604334894502,0.7735491022101784 Atrial septal defect [HP:0001631],42/44,95%,20/20,100%,1.0,1.0 -Short humerus [HP:0005792],7/17,41%,4/9,44%,1.0,1.0 Absent radius [HP:0003974],7/32,22%,6/25,24%,1.0,1.0 -Abnormal atrial septum morphology [HP:0011994],43/43,100%,20/20,100%,, -Abnormal cardiac septum morphology [HP:0001671],62/62,100%,28/28,100%,, -Abnormal heart morphology [HP:0001627],62/62,100%,30/30,100%,, -Abnormal cardiovascular system morphology [HP:0030680],63/63,100%,30/30,100%,, -Abnormality of the cardiovascular system [HP:0001626],65/65,100%,32/32,100%,, +Short humerus [HP:0005792],7/17,41%,4/9,44%,1.0,1.0 +Abnormal carpal morphology [HP:0001191],30/32,94%,0/0,0%,, +Abnormal hand morphology [HP:0005922],53/53,100%,20/20,100%,, +Abnormality of the hand [HP:0001155],60/60,100%,31/31,100%,, +Abnormality of the upper limb [HP:0002817],73/73,100%,34/34,100%,, +Abnormality of limbs [HP:0040064],73/73,100%,34/34,100%,, Phenotypic abnormality [HP:0000118],82/82,100%,38/38,100%,, All [HP:0000001],82/82,100%,38/38,100%,, -Abnormal cardiac atrium morphology [HP:0005120],43/43,100%,20/20,100%,, -Abnormal ventricular septum morphology [HP:0010438],31/31,100%,19/19,100%,, -Abnormal cardiac ventricle morphology [HP:0001713],31/31,100%,19/19,100%,, -Perimembranous ventricular septal defect [HP:0011682],3/59,5%,3/25,12%,, +Abnormality of the wrist [HP:0003019],30/30,100%,0/0,0%,, +Abnormality of upper limb joint [HP:0009810],30/30,100%,6/6,100%,, +Abnormal joint morphology [HP:0001367],31/31,100%,6/6,100%,, +Abnormal skeletal morphology [HP:0011842],73/73,100%,35/35,100%,, +Abnormality of the skeletal system [HP:0000924],73/73,100%,35/35,100%,, +Abnormality of the musculoskeletal system [HP:0033127],74/74,100%,35/35,100%,, Short thumb [HP:0009778],11/41,27%,8/30,27%,, Aplasia/Hypoplasia of the thumb [HP:0009601],20/20,100%,19/19,100%,, Aplasia/Hypoplasia of fingers [HP:0006265],22/22,100%,19/19,100%,, @@ -34,63 +36,49 @@ Aplasia/hypoplasia involving bones of the hand [HP:0005927],22/22,100%,19/19,100 Aplasia/hypoplasia involving bones of the upper limbs [HP:0006496],55/55,100%,22/22,100%,, Aplasia/hypoplasia involving bones of the extremities [HP:0045060],55/55,100%,22/22,100%,, Aplasia/hypoplasia of the extremities [HP:0009815],55/55,100%,22/22,100%,, -Abnormality of limbs [HP:0040064],73/73,100%,34/34,100%,, Aplasia/hypoplasia involving the skeleton [HP:0009115],56/56,100%,23/23,100%,, -Abnormal skeletal morphology [HP:0011842],73/73,100%,35/35,100%,, -Abnormality of the skeletal system [HP:0000924],73/73,100%,35/35,100%,, -Abnormality of the musculoskeletal system [HP:0033127],74/74,100%,35/35,100%,, Abnormal limb bone morphology [HP:0002813],63/63,100%,34/34,100%,, Abnormality of limb bone [HP:0040068],63/63,100%,34/34,100%,, Abnormal appendicular skeleton morphology [HP:0011844],64/64,100%,34/34,100%,, -Abnormality of the upper limb [HP:0002817],73/73,100%,34/34,100%,, -Abnormal hand morphology [HP:0005922],53/53,100%,20/20,100%,, -Abnormality of the hand [HP:0001155],60/60,100%,31/31,100%,, Abnormal finger morphology [HP:0001167],36/36,100%,31/31,100%,, Abnormal digit morphology [HP:0011297],38/38,100%,33/33,100%,, Abnormal thumb morphology [HP:0001172],30/30,100%,31/31,100%,, Short finger [HP:0009381],11/11,100%,8/8,100%,, Short digit [HP:0011927],11/11,100%,10/10,100%,, -Abnormality of thumb phalanx [HP:0009602],13/13,100%,13/13,100%,, -Forearm undergrowth [HP:0009821],30/30,100%,7/7,100%,, -Upper limb undergrowth [HP:0009824],33/33,100%,7/7,100%,, -Limb undergrowth [HP:0009826],33/33,100%,7/7,100%,, +Complete atrioventricular canal defect [HP:0001674],5/37,14%,3/36,8%,, +Atrioventricular canal defect [HP:0006695],5/5,100%,3/3,100%,, +Abnormal cardiac septum morphology [HP:0001671],62/62,100%,28/28,100%,, +Abnormal heart morphology [HP:0001627],62/62,100%,30/30,100%,, +Abnormal cardiovascular system morphology [HP:0030680],63/63,100%,30/30,100%,, +Abnormality of the cardiovascular system [HP:0001626],65/65,100%,32/32,100%,, +11 pairs of ribs [HP:0000878],1/1,100%,0/0,0%,, +Missing ribs [HP:0000921],1/1,100%,0/0,0%,, +Aplasia/Hypoplasia of the ribs [HP:0006712],1/1,100%,0/0,0%,, +Aplasia/Hypoplasia involving bones of the thorax [HP:0006711],1/1,100%,2/2,100%,, +Aplasia/hypoplasia affecting bones of the axial skeleton [HP:0009122],2/2,100%,2/2,100%,, +Abnormal axial skeleton morphology [HP:0009121],8/8,100%,5/5,100%,, +Abnormal thorax morphology [HP:0000765],6/6,100%,5/5,100%,, +Abnormal rib morphology [HP:0000772],1/1,100%,0/0,0%,, +Abnormal rib cage morphology [HP:0001547],4/4,100%,0/0,0%,, +Abnormal cardiac ventricle morphology [HP:0001713],31/31,100%,19/19,100%,, +Abnormal atrial septum morphology [HP:0011994],43/43,100%,20/20,100%,, +Abnormal cardiac atrium morphology [HP:0005120],43/43,100%,20/20,100%,, +Finger aplasia [HP:0009380],15/15,100%,14/14,100%,, +Aplasia involving forearm bones [HP:0009822],7/7,100%,6/6,100%,, Aplasia/hypoplasia involving forearm bones [HP:0006503],37/37,100%,12/12,100%,, Abnormal forearm bone morphology [HP:0040072],37/37,100%,14/14,100%,, Abnormal upper limb bone morphology [HP:0040070],40/40,100%,14/14,100%,, Abnormal forearm morphology [HP:0002973],37/37,100%,14/14,100%,, -Short long bone [HP:0003026],35/35,100%,9/9,100%,, -Abnormal long bone morphology [HP:0011314],44/44,100%,13/13,100%,, Aplasia/Hypoplasia of the radius [HP:0006501],37/37,100%,11/11,100%,, Abnormal morphology of the radius [HP:0002818],37/37,100%,13/13,100%,, -Aplasia of the fingers [HP:0009380],15/15,100%,14/14,100%,, -Tricuspid regurgitation [HP:0005180],3/3,100%,0/0,0%,, -Atrioventricular valve regurgitation [HP:0034376],4/4,100%,2/2,100%,, -Abnormal atrioventricular valve physiology [HP:0031650],4/4,100%,2/2,100%,, -Abnormal heart valve physiology [HP:0031653],4/4,100%,2/2,100%,, -Abnormal cardiovascular system physiology [HP:0011025],23/23,100%,5/5,100%,, -Abnormal tricuspid valve physiology [HP:0031651],3/3,100%,0/0,0%,, -Deviation of the hand or of fingers of the hand [HP:0009484],2/2,100%,2/2,100%,, -Cleft soft palate [HP:0000185],2/2,100%,0/0,0%,, -Abnormal soft palate morphology [HP:0100736],2/2,100%,0/0,0%,, -Abnormal palate morphology [HP:0000174],5/5,100%,0/0,0%,, -Abnormal oral cavity morphology [HP:0000163],5/5,100%,1/1,100%,, -Abnormal oral morphology [HP:0031816],5/5,100%,1/1,100%,, -Abnormality of the mouth [HP:0000153],5/5,100%,1/1,100%,, -Abnormality of the face [HP:0000271],5/5,100%,1/1,100%,, -Abnormality of the head [HP:0000234],5/5,100%,2/2,100%,, -Abnormality of head or neck [HP:0000152],5/5,100%,2/2,100%,, -Cleft palate [HP:0000175],2/2,100%,0/0,0%,, -Orofacial cleft [HP:0000202],2/2,100%,0/0,0%,, -Abnormal carpal morphology [HP:0001191],30/32,94%,0/0,0%,, -Abnormality of the wrist [HP:0003019],30/30,100%,0/0,0%,, -Abnormality of upper limb joint [HP:0009810],30/30,100%,6/6,100%,, -Abnormal joint morphology [HP:0001367],31/31,100%,6/6,100%,, -Mitral valve prolapse [HP:0001634],0/0,0%,1/1,100%,, -Abnormal mitral valve morphology [HP:0001633],0/0,0%,1/1,100%,, -Abnormal atrioventricular valve morphology [HP:0006705],0/0,0%,1/1,100%,, -Abnormal heart valve morphology [HP:0001654],0/0,0%,1/1,100%,, -Mitral regurgitation [HP:0001653],1/1,100%,2/2,100%,, -Abnormal mitral valve physiology [HP:0031481],1/1,100%,2/2,100%,, +Absent forearm bone [HP:0003953],7/7,100%,6/6,100%,, +Forearm undergrowth [HP:0009821],30/30,100%,7/7,100%,, +Upper limb undergrowth [HP:0009824],33/33,100%,7/7,100%,, +Limb undergrowth [HP:0009826],33/33,100%,7/7,100%,, +Short long bone [HP:0003026],35/35,100%,9/9,100%,, +Abnormal long bone morphology [HP:0011314],44/44,100%,13/13,100%,, +Abnormal ventricular septum morphology [HP:0010438],31/31,100%,19/19,100%,, +Abnormality of thumb phalanx [HP:0009602],13/13,100%,13/13,100%,, Limited pronation/supination of forearm [HP:0006394],0/0,0%,3/3,100%,, Limited elbow movement [HP:0002996],0/0,0%,4/4,100%,, Abnormality of the elbow [HP:0009811],0/0,0%,5/5,100%,, @@ -99,8 +87,7 @@ Abnormality of joint mobility [HP:0011729],1/1,100%,5/5,100%,, Abnormal joint physiology [HP:0034430],1/1,100%,5/5,100%,, Abnormal musculoskeletal physiology [HP:0011843],1/1,100%,5/5,100%,, Abnormality of cardiovascular system electrophysiology [HP:0030956],15/15,100%,3/3,100%,, -Upper limb phocomelia [HP:0009813],8/85,9%,2/37,5%,, -Phocomelia [HP:0009829],8/8,100%,2/2,100%,, +Abnormal cardiovascular system physiology [HP:0011025],23/23,100%,5/5,100%,, Pre-capillary pulmonary hypertension [HP:0033578],4/4,100%,0/0,0%,, Elevated pulmonary artery pressure [HP:0004890],4/4,100%,0/0,0%,, Abnormality of pulmonary circulation [HP:0030875],4/4,100%,0/0,0%,, @@ -108,6 +95,11 @@ Abnormal vascular physiology [HP:0030163],4/4,100%,0/0,0%,, Abnormality of the vasculature [HP:0002597],10/10,100%,2/2,100%,, Abnormal respiratory system physiology [HP:0002795],4/4,100%,0/0,0%,, Abnormality of the respiratory system [HP:0002086],4/4,100%,0/0,0%,, +Tricuspid regurgitation [HP:0005180],3/3,100%,0/0,0%,, +Atrioventricular valve regurgitation [HP:0034376],4/4,100%,2/2,100%,, +Abnormal atrioventricular valve physiology [HP:0031650],4/4,100%,2/2,100%,, +Abnormal heart valve physiology [HP:0031653],4/4,100%,2/2,100%,, +Abnormal tricuspid valve physiology [HP:0031651],3/3,100%,0/0,0%,, Aplasia of the 1st metacarpal [HP:0010035],0/0,0%,0/0,0%,, Aplasia of the proximal phalanges of the hand [HP:0010242],0/0,0%,0/0,0%,, Aplasia/Hypoplasia of the proximal phalanges of the hand [HP:0009851],0/0,0%,0/0,0%,, @@ -127,18 +119,25 @@ Partial absence of thumb [HP:0009659],0/0,0%,0/0,0%,, 1-2 finger syndactyly [HP:0010704],3/3,100%,1/1,100%,, Finger syndactyly [HP:0006101],4/4,100%,2/2,100%,, Syndactyly [HP:0001159],4/4,100%,2/2,100%,, -Complete atrioventricular canal defect [HP:0001674],5/37,14%,3/36,8%,, -Atrioventricular canal defect [HP:0006695],5/5,100%,3/3,100%,, -Persistent left superior vena cava [HP:0005301],2/37,5%,0/0,0%,, -Abnormal superior vena cava morphology [HP:0025575],2/2,100%,0/0,0%,, -Abnormal vena cava morphology [HP:0005345],2/2,100%,0/0,0%,, -Abnormal morphology of the great vessels [HP:0030962],6/6,100%,2/2,100%,, -Abnormal blood vessel morphology [HP:0033353],6/6,100%,2/2,100%,, -Abnormal vascular morphology [HP:0025015],6/6,100%,2/2,100%,, -Abnormal venous morphology [HP:0002624],2/2,100%,0/0,0%,, -Abnormal shoulder morphology [HP:0003043],1/1,100%,1/1,100%,, -Abnormal thorax morphology [HP:0000765],6/6,100%,5/5,100%,, -Abnormal axial skeleton morphology [HP:0009121],8/8,100%,5/5,100%,, +Upper limb phocomelia [HP:0009813],8/85,9%,2/37,5%,, +Phocomelia [HP:0009829],8/8,100%,2/2,100%,, +Clinodactyly of the 5th finger [HP:0004209],1/1,100%,0/0,0%,, +Finger clinodactyly [HP:0040019],1/1,100%,0/0,0%,, +Clinodactyly [HP:0030084],1/1,100%,0/0,0%,, +Deviation of finger [HP:0004097],1/1,100%,2/2,100%,, +Deviation of the hand or of fingers of the hand [HP:0009484],2/2,100%,2/2,100%,, +Deviation of the 5th finger [HP:0009179],1/1,100%,0/0,0%,, +Abnormal 5th finger morphology [HP:0004207],4/4,100%,0/0,0%,, +Patent foramen ovale [HP:0001655],4/40,10%,0/36,0%,, +Small hypothenar eminence [HP:0010487],2/2,100%,0/0,0%,, +Abnormality of the hypothenar eminence [HP:0010486],2/2,100%,0/0,0%,, +Abnormality of the musculature of the hand [HP:0001421],2/2,100%,0/0,0%,, +Abnormality of the musculature of the upper limbs [HP:0001446],2/2,100%,0/0,0%,, +Abnormality of the musculature of the limbs [HP:0009127],2/2,100%,0/0,0%,, +Abnormal skeletal muscle morphology [HP:0011805],2/2,100%,0/0,0%,, +Abnormality of the musculature [HP:0003011],2/2,100%,0/0,0%,, +Perimembranous ventricular septal defect [HP:0011682],3/59,5%,3/25,12%,, +Deviation of the thumb [HP:0009603],0/0,0%,2/2,100%,, Aplasia/hypoplasia of the humerus [HP:0006507],7/7,100%,4/4,100%,, Abnormality of the humerus [HP:0003063],7/7,100%,4/4,100%,, Abnormality of the upper arm [HP:0001454],7/7,100%,4/4,100%,, @@ -150,12 +149,18 @@ Abnormal sternum morphology [HP:0000766],3/3,100%,2/2,100%,, Postaxial hand polydactyly [HP:0001162],3/4,75%,0/0,0%,, Postaxial polydactyly [HP:0100259],3/3,100%,0/0,0%,, Polydactyly [HP:0010442],3/3,100%,0/0,0%,, -Abnormal 5th finger morphology [HP:0004207],4/4,100%,0/0,0%,, Hand polydactyly [HP:0001161],3/3,100%,0/0,0%,, Duplication of phalanx of hand [HP:0009997],3/3,100%,0/0,0%,, Duplication of hand bones [HP:0004275],3/3,100%,0/0,0%,, Duplication of bones involving the upper extremities [HP:0009142],3/3,100%,0/0,0%,, High palate [HP:0000218],3/3,100%,0/0,0%,, +Abnormal palate morphology [HP:0000174],5/5,100%,0/0,0%,, +Abnormal oral cavity morphology [HP:0000163],5/5,100%,1/1,100%,, +Abnormal oral morphology [HP:0031816],5/5,100%,1/1,100%,, +Abnormality of the mouth [HP:0000153],5/5,100%,1/1,100%,, +Abnormality of the face [HP:0000271],5/5,100%,1/1,100%,, +Abnormality of the head [HP:0000234],5/5,100%,2/2,100%,, +Abnormality of head or neck [HP:0000152],5/5,100%,2/2,100%,, Short neck [HP:0000470],3/3,100%,0/0,0%,, Abnormal neck morphology [HP:0025668],3/3,100%,0/0,0%,, Abnormality of the neck [HP:0000464],3/3,100%,0/0,0%,, @@ -163,99 +168,95 @@ Abnormality of the cervical spine [HP:0003319],3/3,100%,0/0,0%,, Abnormality of the vertebral column [HP:0000925],4/4,100%,1/1,100%,, Shield chest [HP:0000914],3/3,100%,0/0,0%,, Enlarged thorax [HP:0100625],3/3,100%,0/0,0%,, -Abnormal rib cage morphology [HP:0001547],4/4,100%,0/0,0%,, Y-shaped metatarsals [HP:0010567],3/3,100%,0/0,0%,, Abnormal metatarsal morphology [HP:0001832],3/3,100%,0/0,0%,, Abnormal lower limb bone morphology [HP:0040069],3/3,100%,0/0,0%,, Abnormality of the lower limb [HP:0002814],3/3,100%,0/0,0%,, Abnormal foot morphology [HP:0001760],3/3,100%,0/0,0%,, -Upper extremity joint dislocation [HP:0030310],0/0,0%,2/2,100%,, -Joint dislocation [HP:0001373],0/0,0%,2/2,100%,, -Clinodactyly of the 5th finger [HP:0004209],1/1,100%,0/0,0%,, -Finger clinodactyly [HP:0040019],1/1,100%,0/0,0%,, -Clinodactyly [HP:0030084],1/1,100%,0/0,0%,, -Deviation of finger [HP:0004097],1/1,100%,2/2,100%,, -Deviation of the 5th finger [HP:0009179],1/1,100%,0/0,0%,, -Proximal placement of thumb [HP:0009623],0/0,0%,0/0,0%,, -Deviation of the thumb [HP:0009603],0/0,0%,2/2,100%,, -Abnormal 2nd finger morphology [HP:0004100],1/1,100%,0/0,0%,, -Aplasia/Hypoplasia of the 2nd finger [HP:0006264],1/1,100%,0/0,0%,, -Short middle phalanx of finger [HP:0005819],0/0,0%,0/0,0%,, -Aplasia/Hypoplasia of the middle phalanges of the hand [HP:0009843],0/0,0%,0/0,0%,, -Abnormal middle phalanx morphology of the hand [HP:0009833],0/0,0%,0/0,0%,, -Short phalanx of finger [HP:0009803],0/0,0%,0/0,0%,, -Short middle phalanx of the 5th finger [HP:0004220],0/0,0%,0/0,0%,, -Type A brachydactyly [HP:0009370],0/0,0%,0/0,0%,, -Brachydactyly [HP:0001156],0/0,0%,0/0,0%,, -Short 5th finger [HP:0009237],0/0,0%,0/0,0%,, -Aplasia/Hypoplasia of the 5th finger [HP:0006262],0/0,0%,0/0,0%,, -Aplasia/Hypoplasia of the middle phalanx of the 5th finger [HP:0009161],0/0,0%,0/0,0%,, -Aplasia/Hypoplasia of the phalanges of the 5th finger [HP:0009376],0/0,0%,0/0,0%,, -Abnormal 5th finger phalanx morphology [HP:0004213],0/0,0%,0/0,0%,, -Abnormality of the middle phalanx of the 5th finger [HP:0004219],0/0,0%,0/0,0%,, +Mitral regurgitation [HP:0001653],1/1,100%,2/2,100%,, +Abnormal mitral valve physiology [HP:0031481],1/1,100%,2/2,100%,, +First degree atrioventricular block [HP:0011705],0/22,0%,1/1,100%,, Congenital malformation of the great arteries [HP:0011603],4/4,100%,2/2,100%,, -Aplasia involving forearm bones [HP:0009822],7/7,100%,6/6,100%,, -Absent forearm bone [HP:0003953],7/7,100%,6/6,100%,, -Aplasia/Hypoplasia of the ulna [HP:0006495],2/2,100%,2/2,100%,, +Abnormal morphology of the great vessels [HP:0030962],6/6,100%,2/2,100%,, +Abnormal blood vessel morphology [HP:0033353],6/6,100%,2/2,100%,, +Abnormal vascular morphology [HP:0025015],6/6,100%,2/2,100%,, +Abnormal skull morphology [HP:0000929],1/1,100%,2/2,100%,, +Sinus bradycardia [HP:0001688],0/0,0%,1/1,100%,, +Abnormal electrophysiology of sinoatrial node origin [HP:0011702],0/0,0%,1/1,100%,, +Arrhythmia [HP:0011675],1/1,100%,1/1,100%,, +Bradycardia [HP:0001662],0/0,0%,1/1,100%,, +Abnormal skin morphology [HP:0011121],0/0,0%,1/1,100%,, +Abnormality of the skin [HP:0000951],0/0,0%,1/1,100%,, +Abnormality of the integument [HP:0001574],0/0,0%,1/1,100%,, +Sinus venosus atrial septal defect [HP:0011567],0/2,0%,1/1,100%,, Abnormal morphology of ulna [HP:0040071],2/2,100%,4/4,100%,, +Aplasia/Hypoplasia of the ulna [HP:0006495],2/2,100%,2/2,100%,, +Persistent left superior vena cava [HP:0005301],2/37,5%,0/0,0%,, +Abnormal superior vena cava morphology [HP:0025575],2/2,100%,0/0,0%,, +Abnormal vena cava morphology [HP:0005345],2/2,100%,0/0,0%,, +Abnormal venous morphology [HP:0002624],2/2,100%,0/0,0%,, +Abnormal shoulder morphology [HP:0003043],1/1,100%,1/1,100%,, Hypoplasia of deltoid muscle [HP:0030241],0/0,0%,0/0,0%,, Shoulder muscle hypoplasia [HP:0008952],0/0,0%,0/0,0%,, Hypoplasia of the musculature [HP:0009004],0/0,0%,0/0,0%,, Aplasia/Hypoplasia involving the skeletal musculature [HP:0001460],0/0,0%,0/0,0%,, Abnormality of muscle size [HP:0030236],0/0,0%,0/0,0%,, -Abnormal skeletal muscle morphology [HP:0011805],2/2,100%,0/0,0%,, -Abnormality of the musculature [HP:0003011],2/2,100%,0/0,0%,, Aplasia/Hypoplasia involving the shoulder musculature [HP:0001464],0/0,0%,0/0,0%,, Aplasia/Hypoplasia involving the musculature of the upper limbs [HP:0001467],0/0,0%,0/0,0%,, Aplasia/Hypoplasia involving the musculature of the extremities [HP:0009128],0/0,0%,0/0,0%,, -Abnormality of the musculature of the limbs [HP:0009127],2/2,100%,0/0,0%,, -Abnormality of the musculature of the upper limbs [HP:0001446],2/2,100%,0/0,0%,, Abnormality of the shoulder girdle musculature [HP:0001435],0/0,0%,0/0,0%,, +Common atrium [HP:0011565],0/83,0%,0/38,0%,, +Unroofed coronary sinus [HP:0031297],0/85,0%,0/38,0%,, Atrioventricular dissociation [HP:0011709],0/22,0%,1/1,100%,, -Abnormal toe morphology [HP:0001780],0/0,0%,0/0,0%,, -Abnormal toe phalanx morphology [HP:0010161],0/0,0%,0/0,0%,, -Abnormality of the distal phalanges of the toes [HP:0010182],0/0,0%,0/0,0%,, -Patent foramen ovale [HP:0001655],4/40,10%,0/36,0%,, -Synostosis of joints [HP:0100240],1/1,100%,1/1,100%,, -Short 1st metacarpal [HP:0010034],0/30,0%,0/22,0%,, -Short phalanx of the thumb [HP:0009660],0/30,0%,0/22,0%,, -11 pairs of ribs [HP:0000878],1/1,100%,0/0,0%,, -Missing ribs [HP:0000921],1/1,100%,0/0,0%,, -Aplasia/Hypoplasia of the ribs [HP:0006712],1/1,100%,0/0,0%,, -Aplasia/Hypoplasia involving bones of the thorax [HP:0006711],1/1,100%,2/2,100%,, -Aplasia/hypoplasia affecting bones of the axial skeleton [HP:0009122],2/2,100%,2/2,100%,, -Abnormal rib morphology [HP:0000772],1/1,100%,0/0,0%,, -First degree atrioventricular block [HP:0011705],0/22,0%,1/1,100%,, +Bowed forearm bones [HP:0003956],0/0,0%,1/1,100%,, +Bowing of the arm [HP:0006488],0/0,0%,1/1,100%,, +Bowing of the long bones [HP:0006487],0/0,0%,1/1,100%,, +Abnormal diaphysis morphology [HP:0000940],0/0,0%,1/1,100%,, +Proximal placement of thumb [HP:0009623],0/0,0%,0/0,0%,, +Short middle phalanx of the 5th finger [HP:0004220],0/0,0%,0/0,0%,, +Type A brachydactyly [HP:0009370],0/0,0%,0/0,0%,, +Brachydactyly [HP:0001156],0/0,0%,0/0,0%,, +Short 5th finger [HP:0009237],0/0,0%,0/0,0%,, +Aplasia/Hypoplasia of the 5th finger [HP:0006262],0/0,0%,0/0,0%,, +Aplasia/Hypoplasia of the middle phalanx of the 5th finger [HP:0009161],0/0,0%,0/0,0%,, +Aplasia/Hypoplasia of the phalanges of the 5th finger [HP:0009376],0/0,0%,0/0,0%,, +Abnormal 5th finger phalanx morphology [HP:0004213],0/0,0%,0/0,0%,, +Abnormality of the middle phalanx of the 5th finger [HP:0004219],0/0,0%,0/0,0%,, +Short middle phalanx of finger [HP:0005819],0/0,0%,0/0,0%,, +Aplasia/Hypoplasia of the middle phalanges of the hand [HP:0009843],0/0,0%,0/0,0%,, +Abnormal middle phalanx morphology of the hand [HP:0009833],0/0,0%,0/0,0%,, +Short phalanx of finger [HP:0009803],0/0,0%,0/0,0%,, Micrognathia [HP:0000347],1/1,100%,1/1,100%,, Aplasia/Hypoplasia of the mandible [HP:0009118],1/1,100%,1/1,100%,, Aplasia/Hypoplasia involving bones of the skull [HP:0009116],1/1,100%,1/1,100%,, -Abnormal skull morphology [HP:0000929],1/1,100%,2/2,100%,, Abnormal mandible morphology [HP:0000277],1/1,100%,1/1,100%,, Abnormal jaw morphology [HP:0030791],1/1,100%,1/1,100%,, Abnormal facial skeleton morphology [HP:0011821],1/1,100%,1/1,100%,, -Bowed forearm bones [HP:0003956],0/0,0%,1/1,100%,, -Bowing of the arm [HP:0006488],0/0,0%,1/1,100%,, -Bowing of the long bones [HP:0006487],0/0,0%,1/1,100%,, -Abnormal diaphysis morphology [HP:0000940],0/0,0%,1/1,100%,, -Common atrium [HP:0011565],0/83,0%,0/38,0%,, -Unroofed coronary sinus [HP:0031297],0/85,0%,0/38,0%,, -Amelia involving the upper limbs [HP:0009812],0/83,0%,1/37,3%,, -Third degree atrioventricular block [HP:0001709],0/22,0%,1/1,100%,, -Small hypothenar eminence [HP:0010487],2/2,100%,0/0,0%,, -Abnormality of the hypothenar eminence [HP:0010486],2/2,100%,0/0,0%,, -Abnormality of the musculature of the hand [HP:0001421],2/2,100%,0/0,0%,, +Cleft soft palate [HP:0000185],2/2,100%,0/0,0%,, +Abnormal soft palate morphology [HP:0100736],2/2,100%,0/0,0%,, +Cleft palate [HP:0000175],2/2,100%,0/0,0%,, +Orofacial cleft [HP:0000202],2/2,100%,0/0,0%,, +Craniofacial cleft [HP:5201015],2/2,100%,0/0,0%,, Hypoplastic scapulae [HP:0000882],1/1,100%,1/1,100%,, Aplasia/Hypoplasia of the scapulae [HP:0006713],1/1,100%,1/1,100%,, Abnormal scapula morphology [HP:0000782],1/1,100%,1/1,100%,, +Amelia involving the upper limbs [HP:0009812],0/83,0%,1/37,3%,, +Third degree atrioventricular block [HP:0001709],0/22,0%,1/1,100%,, +Upper extremity joint dislocation [HP:0030310],0/0,0%,2/2,100%,, +Joint dislocation [HP:0001373],0/0,0%,2/2,100%,, +Abnormal toe morphology [HP:0001780],0/0,0%,0/0,0%,, +Abnormal toe phalanx morphology [HP:0010161],0/0,0%,0/0,0%,, +Abnormality of the distal phalanges of the toes [HP:0010182],0/0,0%,0/0,0%,, +Aplasia/Hypoplasia of the 2nd finger [HP:0006264],1/1,100%,0/0,0%,, +Abnormal 2nd finger morphology [HP:0004100],1/1,100%,0/0,0%,, +Synostosis of joints [HP:0100240],1/1,100%,1/1,100%,, Left ventricular noncompaction cardiomyopathy [HP:0011664],0/1,0%,1/5,20%,, Noncompaction cardiomyopathy [HP:0012817],0/0,0%,1/1,100%,, Cardiomyopathy [HP:0001638],0/0,0%,1/1,100%,, Abnormal myocardium morphology [HP:0001637],0/0,0%,1/1,100%,, -Sinus bradycardia [HP:0001688],0/0,0%,1/1,100%,, -Abnormal electrophysiology of sinoatrial node origin [HP:0011702],0/0,0%,1/1,100%,, -Arrhythmia [HP:0011675],1/1,100%,1/1,100%,, -Bradycardia [HP:0001662],0/0,0%,1/1,100%,, -Abnormal skin morphology [HP:0011121],0/0,0%,1/1,100%,, -Abnormality of the skin [HP:0000951],0/0,0%,1/1,100%,, -Abnormality of the integument [HP:0001574],0/0,0%,1/1,100%,, -Sinus venosus atrial septal defect [HP:0011567],0/2,0%,1/1,100%,, +Mitral valve prolapse [HP:0001634],0/0,0%,1/1,100%,, +Abnormal mitral valve morphology [HP:0001633],0/0,0%,1/1,100%,, +Abnormal atrioventricular valve morphology [HP:0006705],0/0,0%,1/1,100%,, +Abnormal heart valve morphology [HP:0001654],0/0,0%,1/1,100%,, +Short 1st metacarpal [HP:0010034],0/30,0%,0/22,0%,, +Short phalanx of the thumb [HP:0009660],0/30,0%,0/22,0%,, diff --git a/docs/report/tbx5_frameshift_vs_missense.mtc_report.html b/docs/report/tbx5_frameshift_vs_missense.mtc_report.html index 783453010..5b149af79 100644 --- a/docs/report/tbx5_frameshift_vs_missense.mtc_report.html +++ b/docs/report/tbx5_frameshift_vs_missense.mtc_report.html @@ -48,9 +48,9 @@

Phenotype testing report

Phenotype MTC filter: HPO MTC filter

Multiple testing correction: fdr_bh

-

Performed statistical tests for 16 out of the total of 259 HPO terms.

+

Performed statistical tests for 16 out of the total of 260 HPO terms.

- + @@ -62,7 +62,7 @@

Phenotype testing report

- + @@ -83,7 +83,7 @@

Phenotype testing report

- + @@ -111,7 +111,7 @@

Phenotype testing report

- + diff --git a/docs/tutorial.rst b/docs/tutorial.rst index a2bc3230a..10ce6a23a 100644 --- a/docs/tutorial.rst +++ b/docs/tutorial.rst @@ -50,11 +50,11 @@ Load HPO ^^^^^^^^ GPSEA needs HPO to do the analysis. -We use HPO toolkit to load HPO version `v2023-10-09`: +We use HPO toolkit to load HPO version `v2024-07-01`: >>> import hpotk ->>> ontology_store = hpotk.configure_ontology_store() ->>> hpo = ontology_store.load_minimal_hpo(release='v2023-10-09') +>>> store = hpotk.configure_ontology_store() +>>> hpo = store.load_minimal_hpo(release='v2024-07-01') .. tip:: @@ -249,12 +249,12 @@ Now we can perform the analysis and investigate the results. 16 We only tested 16 HPO terms. This is despite the individuals being collectively annotated with -259 direct and indirect HPO terms +260 direct and indirect HPO terms >>> len(result.phenotypes) -259 +260 -We can show the reasoning behind *not* testing 243 (`259 - 16`) HPO terms +We can show the reasoning behind *not* testing 244 (`260 - 16`) HPO terms by exploring the phenotype MTC filtering report. >>> from gpsea.view import MtcStatsViewer @@ -266,11 +266,6 @@ by exploring the phenotype MTC filtering report. .. raw:: html :file: report/tbx5_frameshift_vs_missense.mtc_report.html -.. - - TODO: - Show how to write out the tested HPO terms. - and these are the HPO terms ordered by the p value corrected with the Benjamini-Hochberg procedure: >>> from gpsea.analysis.predicate import PatientCategories diff --git a/docs/user-guide/input-data.rst b/docs/user-guide/input-data.rst index 646df52aa..f04132955 100644 --- a/docs/user-guide/input-data.rst +++ b/docs/user-guide/input-data.rst @@ -32,7 +32,7 @@ the standard `gpsea` installation: >>> import hpotk >>> store = hpotk.configure_ontology_store() ->>> hpo = store.load_minimal_hpo(release='v2024-03-06') +>>> hpo = store.load_minimal_hpo(release='v2024-07-01') Next, let's prepare a :class:`~gpsea.preprocessing.CohortCreator` that will turn a collection of phenopacket into a :class:`~gpsea.model.Cohort`, required in the downstream steps. diff --git a/docs/user-guide/mtc.rst b/docs/user-guide/mtc.rst index 7aa3e23e3..f8958b8ae 100644 --- a/docs/user-guide/mtc.rst +++ b/docs/user-guide/mtc.rst @@ -4,8 +4,9 @@ Multiple-testing correction =========================== +********** Background -~~~~~~~~~~ +********** A p-value is the probability that a test result, under the null hypothesis, assumes the observed or a more extreme value. It is important to realize that if we @@ -25,33 +26,28 @@ tests, the probability that none will be significant is least one significant result. +*********************** Implementation in GPSEA -~~~~~~~~~~~~~~~~~~~~~~~ +*********************** By default, GPSEA performs a hypothesis test for each HPO term found at least twice in the cohort, meaning that we may perform up to hundreds of tests. Therefore, unless we take into account the fact that multiple statistical tests are being performed, it is likely that we will obtain one or more false-positive results. -Genephenocorr offers two approaches to mitigate this problem: multiple-testing correction (MTC) procedures +GPSEA offers two approaches to mitigate this problem: multiple-testing correction (MTC) procedures and MTC filters to choose the terms to be tested. -Here we will show how to configure the MTC approach -using :class:`~gpsea.analysis.CohortAnalysisConfiguration` class. - ->>> from gpsea.analysis import CohortAnalysisConfiguration ->>> config = CohortAnalysisConfiguration() - Multiple-testing correction procedures -^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ +====================================== A number of MTC procedures have been developed to limit the probability of false-positive results. The MTC procedures differ in complexity, in their assumptions about the data, and in the type of control they provide. -The genephenocorr package uses the Python package `statsmodels `_ to implement +The GPSEA package uses the Python package `statsmodels `_ to implement MTC. See the `documentation `_ for details; the following table shows allowable options. @@ -83,31 +79,35 @@ the following table shows allowable options. The oldest and simplest MTC procedure is the Bonferroni -correction. The Bonferroni procedure thus provides control of the family-wise +correction (``bonferroni``). The Bonferroni procedure thus provides control of the family-wise error rate (FWER), which is the probability of at least one Type I error. The Bonferroni method multiplies the p-value returned by each test (which is call the *nominal* p-value) -by the number of tests performed (the result is capped at 1.0). This is the *default* method in genephenocorr. - ->>> config.pval_correction -'bonferroni' +by the number of tests performed (the result is capped at 1.0). Alternatively, procedures that control the false-discovery rate (FDR), limit the proportion of significant results that are type I errors (false discoveries). The Benjamini and Hochberg method (``fdr_bh``) is probably the most commonly used one. - -This is how we can set an alternative MTC correction procedure: - ->>> config.pval_correction = 'fdr_bh' ->>> config.pval_correction -'fdr_bh' +This is the *default* method in GPSEA. + +To set an alternative MTC procedure, we use the `mtc_correction` option +when creating an instance of :class:`~gpsea.analysis.pcats.HpoTermAnalysis`: + +>>> from gpsea.analysis.mtc_filter import UseAllTermsMtcFilter +>>> from gpsea.analysis.pcats import HpoTermAnalysis +>>> from gpsea.analysis.pcats.stats import ScipyFisherExact +>>> analysis = HpoTermAnalysis( +... count_statistic=ScipyFisherExact(), +... mtc_filter=UseAllTermsMtcFilter(), +... mtc_correction='bonferroni', # <--- The MTC correction setup +... ) .. _mtc-filters: MTC filters: Choosing which terms to test -^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ +========================================= We can reduce the overall MTC burden by choosing which terms to test. For example, if we choose to test only ten terms out of 450, @@ -116,8 +116,19 @@ is only 10 instead of 450, and more p-values may "survive" the multiple-testing correction. In the context of GPSEA, we represent the concept of phenotype filtering -by :class:`~gpsea.analysis.PhenotypeMtcFilter`. -We describe the three filtering strategies in the next sections. +by :class:`~gpsea.analysis.mtc_filter.PhenotypeMtcFilter`. +The filter must be chosen before the :class:`~gpsea.analysis.pcats.MultiPhenotypeAnalysis`, +such as :class:`~gpsea.analysis.pcats.HpoTermAnalysis`, is run: + +>>> from gpsea.analysis.pcats import HpoTermAnalysis +>>> analysis = HpoTermAnalysis() # doctest: +ELLIPSIS +Traceback (most recent call last): + ... +TypeError: HpoTermAnalysis.__init__() missing 2 required positional arguments: 'count_statistic' and 'mtc_filter' + +Note the missing `mtc_filter` option. + +We describe the three filtering strategies in the following sections. .. _use-all-terms-strategy: @@ -129,13 +140,10 @@ The first MTC filtering strategy is the simplest - do not apply any filtering at This will result in testing all terms. We do not recommend this strategy, but it can be useful to disable MTC filtering. -The strategy is invoked by default, -or explicitly by :func:`~gpsea.analysis.CohortAnalysisConfiguration.all_terms_strategy` method: - ->>> config.all_terms_strategy() ->>> config.mtc_strategy - +The strategy is implemented in :class:`~gpsea.analysis.mtc_filter.UseAllTermsMtcFilter`. +>>> from gpsea.analysis.mtc_filter import UseAllTermsMtcFilter +>>> use_all = UseAllTermsMtcFilter() .. _specify-terms-strategy: @@ -143,27 +151,20 @@ Specify terms strategy ---------------------- In presence of a specific hypothesis as to which terms may be different between groups, -then you can specify these terms using -the :func:`~gpsea.analysis.CohortAnalysisConfiguration.specify_terms_strategy` method. +then you can specify these terms in :class:`~gpsea.analysis.mtc_filter.SpecifiedTermsMtcFilter`. For example if we want to specifically test `Abnormal putamen morphology (HP:0031982) `_ and `Abnormal caudate nucleus morphology (HP:0002339) `_ we pass an iterable (e.g. a tuple) with these two terms as an argument: ->>> config.specify_terms_strategy( +>>> from gpsea.analysis.mtc_filter import SpecifiedTermsMtcFilter +>>> specified_terms = SpecifiedTermsMtcFilter( ... terms_to_test=( ... "HP:0031982", # Abnormal putamen morphology ... "HP:0002339", # Abnormal caudate nucleus morphology ... ) ... ) ->>> config.mtc_strategy - ->>> config.terms_to_test -('HP:0031982', 'HP:0002339') - -Later, when the `config` is used in analysis, -GPSEA will only perform two hypothesis tests, one for each of the two terms. .. _hpo-mtc-filter-strategy: @@ -172,26 +173,32 @@ HPO MTC filter strategy ----------------------- Last, the HPO MTC strategy involves making several domain judgments to take advantage of the HPO structure. +The strategy needs access to HPO: -The strategy is chosen by invoking -:func:`~gpsea.analysis.CohortAnalysisConfiguration.hpo_mtc_strategy` method: +>>> import hpotk +>>> store = hpotk.configure_ontology_store() +>>> hpo = store.load_minimal_hpo(release='v2024-07-01') + +and it is implemented in the :class:`~gpsea.analysis.mtc_filter.HpoMtcFilter` class: + +>>> from gpsea.analysis.mtc_filter import HpoMtcFilter +>>> hpo_mtc = HpoMtcFilter.default_filter( +... hpo=hpo, +... term_frequency_threshold=0.2, +... ) ->>> config = CohortAnalysisConfiguration() ->>> config.hpo_mtc_strategy(min_patients_w_hpo=0.5) ->>> config.mtc_strategy - ->>> config.min_patients_w_hpo -0.5 -HPO MTC takes a threshold as an argument (e.g. 50% in the example above) +We use static constructor :func:`~gpsea.analysis.mtc_filter.HpoMtcFilter.default_filter` +for creating :class:`~gpsea.analysis.mtc_filter.HpoMtcFilter`. +The constructor takes a threshold as an argument (e.g. 20% in the example above) and the method's logic is made up of 8 individual heuristics designed to skip testing the HPO terms that are unlikely to yield significant or interesting results: #. Skip terms that occur very rarely - The ``min_patients_w_hpo`` determines the mininum proportion of individuals + The ``term_frequency_threshold`` determines the mininum proportion of individuals with direct or indirect annotation by the HPO term to test. We check each of the genotype groups (e.g., MISSENSE vs. not-MISSENSE), and we only retain a term for testing - if the proportion of individuals in at least one genotype group is at least ``min_patients_w_hpo``. + if the proportion of individuals in at least one genotype group is greater than or equal to ``term_frequency_threshold``. This is because of our assumption that even if there is statistical significance, if a term is only seen in (for example) 7% of individuals in the MISSENSE group and 2% in the not-MISSENSE group, diff --git a/docs/user-guide/predicates.rst b/docs/user-guide/predicates.rst index e3393847e..00647f1f2 100644 --- a/docs/user-guide/predicates.rst +++ b/docs/user-guide/predicates.rst @@ -27,7 +27,7 @@ Briefly, we first load HPO: >>> import hpotk >>> store = hpotk.configure_ontology_store() ->>> hpo = store.load_minimal_hpo(release='v2024-03-06') +>>> hpo = store.load_minimal_hpo(release='v2024-07-01') then, we configure the cohort creator: diff --git a/docs/user-guide/report/tbx5_frameshift.csv b/docs/user-guide/report/tbx5_frameshift.csv index d794cec44..6abe64be2 100644 --- a/docs/user-guide/report/tbx5_frameshift.csv +++ b/docs/user-guide/report/tbx5_frameshift.csv @@ -13,42 +13,148 @@ Muscular ventricular septal defect [HP:0011623],6/25,24%,8/84,10%,0.144002047919 Pulmonary arterial hypertension [HP:0002092],0/2,0%,8/14,57%,0.6899307928951144,0.4666666666666667 Short thumb [HP:0009778],8/30,27%,25/69,36%,0.6899307928951144,0.4870099714553749 Absent radius [HP:0003974],6/25,24%,9/43,21%,1.0,0.7703831604944444 -Atrial septal defect [HP:0001631],20/20,100%,63/65,97%,1.0,1.0 Hypoplasia of the radius [HP:0002984],6/14,43%,34/75,45%,1.0,1.0 -Short humerus [HP:0005792],4/9,44%,8/21,38%,1.0,1.0 +Atrial septal defect [HP:0001631],20/20,100%,63/65,97%,1.0,1.0 Hypoplasia of the ulna [HP:0003022],2/10,20%,3/17,18%,1.0,1.0 -Aplasia/Hypoplasia of the thumb [HP:0009601],19/19,100%,40/40,100%,, -Aplasia/Hypoplasia of fingers [HP:0006265],19/19,100%,44/44,100%,, -Aplasia/hypoplasia involving bones of the hand [HP:0005927],19/19,100%,44/44,100%,, -Aplasia/hypoplasia involving bones of the upper limbs [HP:0006496],22/22,100%,78/78,100%,, -Aplasia/hypoplasia involving bones of the extremities [HP:0045060],22/22,100%,78/78,100%,, -Aplasia/hypoplasia of the extremities [HP:0009815],22/22,100%,78/78,100%,, -Abnormality of limbs [HP:0040064],34/34,100%,102/102,100%,, +Short humerus [HP:0005792],4/9,44%,8/21,38%,1.0,1.0 +Abnormal ventricular septum morphology [HP:0010438],19/19,100%,42/42,100%,, +Abnormal cardiac ventricle morphology [HP:0001713],19/19,100%,43/43,100%,, +Abnormal heart morphology [HP:0001627],30/30,100%,89/89,100%,, +Abnormal cardiovascular system morphology [HP:0030680],30/30,100%,92/92,100%,, +Abnormality of the cardiovascular system [HP:0001626],32/32,100%,94/94,100%,, Phenotypic abnormality [HP:0000118],38/38,100%,114/114,100%,, All [HP:0000001],38/38,100%,114/114,100%,, -Aplasia/hypoplasia involving the skeleton [HP:0009115],23/23,100%,80/80,100%,, -Abnormal skeletal morphology [HP:0011842],35/35,100%,103/103,100%,, -Abnormality of the skeletal system [HP:0000924],35/35,100%,103/103,100%,, -Abnormality of the musculoskeletal system [HP:0033127],35/35,100%,104/104,100%,, +Abnormal cardiac septum morphology [HP:0001671],28/28,100%,89/89,100%,, +Forearm undergrowth [HP:0009821],7/7,100%,35/35,100%,, +Abnormal upper limb bone morphology [HP:0040070],14/14,100%,50/50,100%,, +Abnormality of the upper limb [HP:0002817],34/34,100%,102/102,100%,, +Abnormality of limbs [HP:0040064],34/34,100%,102/102,100%,, Abnormal limb bone morphology [HP:0002813],34/34,100%,92/92,100%,, Abnormality of limb bone [HP:0040068],34/34,100%,92/92,100%,, +Abnormality of the skeletal system [HP:0000924],35/35,100%,103/103,100%,, +Abnormality of the musculoskeletal system [HP:0033127],35/35,100%,104/104,100%,, Abnormal appendicular skeleton morphology [HP:0011844],34/34,100%,93/93,100%,, -Abnormality of the upper limb [HP:0002817],34/34,100%,102/102,100%,, +Abnormal skeletal morphology [HP:0011842],35/35,100%,103/103,100%,, +Upper limb undergrowth [HP:0009824],7/7,100%,38/38,100%,, +Limb undergrowth [HP:0009826],7/7,100%,38/38,100%,, +Aplasia/hypoplasia of the extremities [HP:0009815],22/22,100%,78/78,100%,, +Aplasia/hypoplasia involving the skeleton [HP:0009115],23/23,100%,80/80,100%,, +Aplasia/hypoplasia involving bones of the upper limbs [HP:0006496],22/22,100%,78/78,100%,, +Aplasia/hypoplasia involving bones of the extremities [HP:0045060],22/22,100%,78/78,100%,, +Aplasia/hypoplasia involving forearm bones [HP:0006503],12/12,100%,43/43,100%,, +Abnormal forearm bone morphology [HP:0040072],14/14,100%,43/43,100%,, +Abnormal forearm morphology [HP:0002973],14/14,100%,43/43,100%,, +Short long bone [HP:0003026],9/9,100%,41/41,100%,, +Abnormal long bone morphology [HP:0011314],13/13,100%,50/50,100%,, +Aplasia/Hypoplasia of the radius [HP:0006501],11/11,100%,43/43,100%,, +Abnormal morphology of the radius [HP:0002818],13/13,100%,43/43,100%,, +1-2 finger syndactyly [HP:0010704],1/1,100%,4/4,100%,, +Finger syndactyly [HP:0006101],2/2,100%,5/5,100%,, +Syndactyly [HP:0001159],2/2,100%,5/5,100%,, +Abnormal digit morphology [HP:0011297],33/33,100%,67/67,100%,, +Abnormal atrial septum morphology [HP:0011994],20/20,100%,64/64,100%,, +Abnormal cardiac atrium morphology [HP:0005120],20/20,100%,64/64,100%,, +Perimembranous ventricular septal defect [HP:0011682],3/25,12%,6/84,7%,, +Aplasia/Hypoplasia of the thumb [HP:0009601],19/19,100%,40/40,100%,, +Aplasia/Hypoplasia of fingers [HP:0006265],19/19,100%,44/44,100%,, +Aplasia/hypoplasia involving bones of the hand [HP:0005927],19/19,100%,44/44,100%,, Abnormal hand morphology [HP:0005922],20/20,100%,75/75,100%,, Abnormality of the hand [HP:0001155],31/31,100%,88/88,100%,, Abnormal finger morphology [HP:0001167],31/31,100%,64/64,100%,, -Abnormal digit morphology [HP:0011297],33/33,100%,67/67,100%,, Abnormal thumb morphology [HP:0001172],31/31,100%,58/58,100%,, +Finger aplasia [HP:0009380],14/14,100%,23/23,100%,, +Aplasia involving forearm bones [HP:0009822],6/6,100%,9/9,100%,, +Absent forearm bone [HP:0003953],6/6,100%,9/9,100%,, +Aplasia/Hypoplasia of the ulna [HP:0006495],2/2,100%,4/4,100%,, +Abnormal morphology of ulna [HP:0040071],4/4,100%,4/4,100%,, +Abnormal carpal morphology [HP:0001191],0/0,0%,30/32,94%,, +Abnormality of the wrist [HP:0003019],0/0,0%,30/30,100%,, +Abnormality of upper limb joint [HP:0009810],6/6,100%,32/32,100%,, +Abnormal joint morphology [HP:0001367],6/6,100%,33/33,100%,, +Abnormality of cardiovascular system electrophysiology [HP:0030956],3/3,100%,18/18,100%,, +Abnormal cardiovascular system physiology [HP:0011025],5/5,100%,30/30,100%,, +Abnormality of thumb phalanx [HP:0009602],13/13,100%,26/26,100%,, +Upper limb phocomelia [HP:0009813],2/37,5%,8/116,7%,, +Phocomelia [HP:0009829],2/2,100%,8/8,100%,, Short finger [HP:0009381],8/8,100%,27/27,100%,, Short digit [HP:0011927],10/10,100%,28/28,100%,, -Abnormality of thumb phalanx [HP:0009602],13/13,100%,26/26,100%,, +Pre-capillary pulmonary hypertension [HP:0033578],0/0,0%,8/8,100%,, +Elevated pulmonary artery pressure [HP:0004890],0/0,0%,8/8,100%,, +Abnormality of pulmonary circulation [HP:0030875],0/0,0%,8/8,100%,, +Abnormal vascular physiology [HP:0030163],0/0,0%,8/8,100%,, +Abnormality of the vasculature [HP:0002597],2/2,100%,17/17,100%,, +Abnormal respiratory system physiology [HP:0002795],0/0,0%,8/8,100%,, +Abnormality of the respiratory system [HP:0002086],0/0,0%,8/8,100%,, Congenital malformation of the great arteries [HP:0011603],2/2,100%,7/7,100%,, Abnormal morphology of the great vessels [HP:0030962],2/2,100%,10/10,100%,, Abnormal blood vessel morphology [HP:0033353],2/2,100%,11/11,100%,, Abnormal vascular morphology [HP:0025015],2/2,100%,11/11,100%,, -Abnormal cardiovascular system morphology [HP:0030680],30/30,100%,92/92,100%,, -Abnormality of the cardiovascular system [HP:0001626],32/32,100%,94/94,100%,, -Abnormality of the vasculature [HP:0002597],2/2,100%,17/17,100%,, +Patent foramen ovale [HP:0001655],0/36,0%,4/69,6%,, +Synostosis of joints [HP:0100240],1/1,100%,1/1,100%,, +Abnormality of joint mobility [HP:0011729],5/5,100%,3/3,100%,, +Abnormal joint physiology [HP:0034430],5/5,100%,3/3,100%,, +Abnormal musculoskeletal physiology [HP:0011843],5/5,100%,3/3,100%,, +Abnormality of the vertebral column [HP:0000925],1/1,100%,4/4,100%,, +Abnormal axial skeleton morphology [HP:0009121],5/5,100%,9/9,100%,, +Complete atrioventricular canal defect [HP:0001674],3/36,8%,6/67,9%,, +Atrioventricular canal defect [HP:0006695],3/3,100%,6/6,100%,, +Hypoplasia of deltoid muscle [HP:0030241],0/0,0%,6/6,100%,, +Shoulder muscle hypoplasia [HP:0008952],0/0,0%,6/6,100%,, +Hypoplasia of the musculature [HP:0009004],0/0,0%,6/6,100%,, +Aplasia/Hypoplasia involving the skeletal musculature [HP:0001460],0/0,0%,6/6,100%,, +Abnormality of muscle size [HP:0030236],0/0,0%,6/6,100%,, +Abnormal skeletal muscle morphology [HP:0011805],0/0,0%,8/8,100%,, +Abnormality of the musculature [HP:0003011],0/0,0%,8/8,100%,, +Aplasia/Hypoplasia involving the shoulder musculature [HP:0001464],0/0,0%,6/6,100%,, +Aplasia/Hypoplasia involving the musculature of the upper limbs [HP:0001467],0/0,0%,6/6,100%,, +Aplasia/Hypoplasia involving the musculature of the extremities [HP:0009128],0/0,0%,6/6,100%,, +Abnormality of the musculature of the limbs [HP:0009127],0/0,0%,8/8,100%,, +Abnormality of the musculature of the upper limbs [HP:0001446],0/0,0%,8/8,100%,, +Abnormality of the shoulder girdle musculature [HP:0001435],0/0,0%,6/6,100%,, +Bowed forearm bones [HP:0003956],1/1,100%,0/0,0%,, +Bowing of the arm [HP:0006488],1/1,100%,0/0,0%,, +Bowing of the long bones [HP:0006487],1/1,100%,0/0,0%,, +Abnormal diaphysis morphology [HP:0000940],1/1,100%,0/0,0%,, +Micrognathia [HP:0000347],1/1,100%,1/1,100%,, +Aplasia/Hypoplasia of the mandible [HP:0009118],1/1,100%,1/1,100%,, +Aplasia/Hypoplasia involving bones of the skull [HP:0009116],1/1,100%,1/1,100%,, +Aplasia/hypoplasia affecting bones of the axial skeleton [HP:0009122],2/2,100%,3/3,100%,, +Abnormal skull morphology [HP:0000929],2/2,100%,1/1,100%,, +Abnormality of the head [HP:0000234],2/2,100%,5/5,100%,, +Abnormality of head or neck [HP:0000152],2/2,100%,5/5,100%,, +Abnormal mandible morphology [HP:0000277],1/1,100%,1/1,100%,, +Abnormal jaw morphology [HP:0030791],1/1,100%,1/1,100%,, +Abnormal facial skeleton morphology [HP:0011821],1/1,100%,1/1,100%,, +Abnormal oral cavity morphology [HP:0000163],1/1,100%,5/5,100%,, +Abnormal oral morphology [HP:0031816],1/1,100%,5/5,100%,, +Abnormality of the mouth [HP:0000153],1/1,100%,5/5,100%,, +Abnormality of the face [HP:0000271],1/1,100%,5/5,100%,, +Aplasia/Hypoplasia involving bones of the thorax [HP:0006711],2/2,100%,2/2,100%,, +Abnormal thorax morphology [HP:0000765],5/5,100%,7/7,100%,, +Persistent left superior vena cava [HP:0005301],0/0,0%,4/39,10%,, +Abnormal superior vena cava morphology [HP:0025575],0/0,0%,4/4,100%,, +Abnormal vena cava morphology [HP:0005345],0/0,0%,4/4,100%,, +Abnormal venous morphology [HP:0002624],0/0,0%,4/4,100%,, +Aplasia/hypoplasia of the humerus [HP:0006507],4/4,100%,8/8,100%,, +Abnormality of the humerus [HP:0003063],4/4,100%,8/8,100%,, +Abnormality of the upper arm [HP:0001454],4/4,100%,8/8,100%,, +Right atrial enlargement [HP:0030718],0/0,0%,4/4,100%,, +Abnormal right atrium morphology [HP:0025580],0/0,0%,4/4,100%,, +Atrial septal dilatation [HP:0011995],0/0,0%,4/4,100%,, +Left ventricular noncompaction cardiomyopathy [HP:0011664],1/5,20%,1/7,14%,, +Noncompaction cardiomyopathy [HP:0012817],1/1,100%,1/1,100%,, +Cardiomyopathy [HP:0001638],1/1,100%,1/1,100%,, +Abnormal myocardium morphology [HP:0001637],1/1,100%,1/1,100%,, +Hypoplastic scapulae [HP:0000882],1/1,100%,1/1,100%,, +Aplasia/Hypoplasia of the scapulae [HP:0006713],1/1,100%,1/1,100%,, +Abnormal scapula morphology [HP:0000782],1/1,100%,1/1,100%,, +Abnormal toe morphology [HP:0001780],0/0,0%,1/1,100%,, +Abnormal foot morphology [HP:0001760],0/0,0%,4/4,100%,, +Abnormality of the lower limb [HP:0002814],0/0,0%,4/4,100%,, +Abnormal toe phalanx morphology [HP:0010161],0/0,0%,1/1,100%,, +Abnormality of the distal phalanges of the toes [HP:0010182],0/0,0%,1/1,100%,, +Abnormal lower limb bone morphology [HP:0040069],0/0,0%,4/4,100%,, +Aplasia involving bones of the extremities [HP:0009825],0/0,0%,3/3,100%,, Aplasia of the 1st metacarpal [HP:0010035],0/0,0%,3/3,100%,, Aplasia of the proximal phalanges of the hand [HP:0010242],0/0,0%,3/3,100%,, Aplasia/Hypoplasia of the proximal phalanges of the hand [HP:0009851],0/0,0%,3/3,100%,, @@ -57,137 +163,44 @@ Abnormal finger phalanx morphology [HP:0005918],0/0,0%,9/9,100%,, Aplasia/Hypoplasia of the phalanges of the hand [HP:0009767],0/0,0%,6/6,100%,, Aplasia of the phalanges of the hand [HP:0009802],0/0,0%,3/3,100%,, Aplasia involving bones of the upper limbs [HP:0009823],0/0,0%,3/3,100%,, -Aplasia involving bones of the extremities [HP:0009825],0/0,0%,3/3,100%,, -Finger aplasia [HP:0009380],14/14,100%,23/23,100%,, Aplasia of metacarpal bones [HP:0010048],0/0,0%,3/3,100%,, Aplasia/Hypoplasia involving the metacarpal bones [HP:0005914],0/0,0%,4/4,100%,, Abnormal metacarpal morphology [HP:0005916],0/0,0%,4/4,100%,, -Abnormal upper limb bone morphology [HP:0040070],14/14,100%,50/50,100%,, Aplasia/Hypoplasia of the 1st metacarpal [HP:0010026],0/0,0%,4/4,100%,, Abnormal 1st metacarpal morphology [HP:0010009],0/0,0%,4/4,100%,, Aplasia/Hypoplasia of the phalanges of the thumb [HP:0009658],0/0,0%,4/4,100%,, Partial absence of thumb [HP:0009659],0/0,0%,3/3,100%,, -Abnormal atrial septum morphology [HP:0011994],20/20,100%,64/64,100%,, -Abnormal cardiac septum morphology [HP:0001671],28/28,100%,89/89,100%,, -Abnormal heart morphology [HP:0001627],30/30,100%,89/89,100%,, -Abnormal cardiac atrium morphology [HP:0005120],20/20,100%,64/64,100%,, -Perimembranous ventricular septal defect [HP:0011682],3/25,12%,6/84,7%,, -Abnormal ventricular septum morphology [HP:0010438],19/19,100%,42/42,100%,, -Abnormal cardiac ventricle morphology [HP:0001713],19/19,100%,43/43,100%,, -Forearm undergrowth [HP:0009821],7/7,100%,35/35,100%,, -Upper limb undergrowth [HP:0009824],7/7,100%,38/38,100%,, -Limb undergrowth [HP:0009826],7/7,100%,38/38,100%,, -Aplasia/hypoplasia involving forearm bones [HP:0006503],12/12,100%,43/43,100%,, -Abnormal forearm bone morphology [HP:0040072],14/14,100%,43/43,100%,, -Abnormal forearm morphology [HP:0002973],14/14,100%,43/43,100%,, -Short long bone [HP:0003026],9/9,100%,41/41,100%,, -Abnormal long bone morphology [HP:0011314],13/13,100%,50/50,100%,, -Aplasia/Hypoplasia of the radius [HP:0006501],11/11,100%,43/43,100%,, -Abnormal morphology of the radius [HP:0002818],13/13,100%,43/43,100%,, -Abnormal carpal morphology [HP:0001191],0/0,0%,30/32,94%,, -Abnormality of the wrist [HP:0003019],0/0,0%,30/30,100%,, -Abnormality of upper limb joint [HP:0009810],6/6,100%,32/32,100%,, -Abnormal joint morphology [HP:0001367],6/6,100%,33/33,100%,, -Persistent left superior vena cava [HP:0005301],0/0,0%,4/39,10%,, -Abnormal superior vena cava morphology [HP:0025575],0/0,0%,4/4,100%,, -Abnormal vena cava morphology [HP:0005345],0/0,0%,4/4,100%,, -Abnormal venous morphology [HP:0002624],0/0,0%,4/4,100%,, -Tricuspid regurgitation [HP:0005180],0/0,0%,5/5,100%,, +Limited pronation/supination of forearm [HP:0006394],3/3,100%,2/2,100%,, +Limited elbow movement [HP:0002996],4/4,100%,2/2,100%,, +Abnormality of the elbow [HP:0009811],5/5,100%,2/2,100%,, +Limitation of joint mobility [HP:0001376],4/4,100%,2/2,100%,, +Mitral regurgitation [HP:0001653],2/2,100%,2/2,100%,, Atrioventricular valve regurgitation [HP:0034376],2/2,100%,7/7,100%,, Abnormal atrioventricular valve physiology [HP:0031650],2/2,100%,7/7,100%,, Abnormal heart valve physiology [HP:0031653],2/2,100%,7/7,100%,, -Abnormal cardiovascular system physiology [HP:0011025],5/5,100%,30/30,100%,, +Abnormal mitral valve physiology [HP:0031481],2/2,100%,2/2,100%,, +Tricuspid regurgitation [HP:0005180],0/0,0%,5/5,100%,, Abnormal tricuspid valve physiology [HP:0031651],0/0,0%,5/5,100%,, -Micrognathia [HP:0000347],1/1,100%,1/1,100%,, -Aplasia/Hypoplasia of the mandible [HP:0009118],1/1,100%,1/1,100%,, -Aplasia/Hypoplasia involving bones of the skull [HP:0009116],1/1,100%,1/1,100%,, -Aplasia/hypoplasia affecting bones of the axial skeleton [HP:0009122],2/2,100%,3/3,100%,, -Abnormal axial skeleton morphology [HP:0009121],5/5,100%,9/9,100%,, -Abnormal skull morphology [HP:0000929],2/2,100%,1/1,100%,, -Abnormality of the head [HP:0000234],2/2,100%,5/5,100%,, -Abnormality of head or neck [HP:0000152],2/2,100%,5/5,100%,, -Abnormal mandible morphology [HP:0000277],1/1,100%,1/1,100%,, -Abnormal jaw morphology [HP:0030791],1/1,100%,1/1,100%,, -Abnormal facial skeleton morphology [HP:0011821],1/1,100%,1/1,100%,, Cleft soft palate [HP:0000185],0/0,0%,2/2,100%,, Abnormal soft palate morphology [HP:0100736],0/0,0%,2/2,100%,, Abnormal palate morphology [HP:0000174],0/0,0%,5/5,100%,, -Abnormal oral cavity morphology [HP:0000163],1/1,100%,5/5,100%,, -Abnormal oral morphology [HP:0031816],1/1,100%,5/5,100%,, -Abnormality of the mouth [HP:0000153],1/1,100%,5/5,100%,, -Abnormality of the face [HP:0000271],1/1,100%,5/5,100%,, Cleft palate [HP:0000175],0/0,0%,2/2,100%,, Orofacial cleft [HP:0000202],0/0,0%,2/2,100%,, Craniofacial cleft [HP:5201015],0/0,0%,2/2,100%,, -Aplasia involving forearm bones [HP:0009822],6/6,100%,9/9,100%,, -Absent forearm bone [HP:0003953],6/6,100%,9/9,100%,, -Aplasia/hypoplasia of the humerus [HP:0006507],4/4,100%,8/8,100%,, -Abnormality of the humerus [HP:0003063],4/4,100%,8/8,100%,, -Abnormality of the upper arm [HP:0001454],4/4,100%,8/8,100%,, -1-2 finger syndactyly [HP:0010704],1/1,100%,4/4,100%,, -Finger syndactyly [HP:0006101],2/2,100%,5/5,100%,, -Syndactyly [HP:0001159],2/2,100%,5/5,100%,, -Complete atrioventricular canal defect [HP:0001674],3/36,8%,6/67,9%,, -Atrioventricular canal defect [HP:0006695],3/3,100%,6/6,100%,, -Upper limb phocomelia [HP:0009813],2/37,5%,8/116,7%,, -Phocomelia [HP:0009829],2/2,100%,8/8,100%,, -Abnormality of cardiovascular system electrophysiology [HP:0030956],3/3,100%,18/18,100%,, -Atrioventricular dissociation [HP:0011709],1/1,100%,0/22,0%,, -Abnormal morphology of ulna [HP:0040071],4/4,100%,4/4,100%,, -Aplasia/Hypoplasia of the ulna [HP:0006495],2/2,100%,4/4,100%,, -Mitral valve prolapse [HP:0001634],1/1,100%,1/1,100%,, -Abnormal mitral valve morphology [HP:0001633],1/1,100%,1/1,100%,, -Abnormal atrioventricular valve morphology [HP:0006705],1/1,100%,1/1,100%,, -Abnormal heart valve morphology [HP:0001654],1/1,100%,1/1,100%,, -Proximal placement of thumb [HP:0009623],0/0,0%,3/3,100%,, -Deviation of the thumb [HP:0009603],2/2,100%,3/3,100%,, -Deviation of finger [HP:0004097],2/2,100%,4/4,100%,, -Deviation of the hand or of fingers of the hand [HP:0009484],2/2,100%,5/5,100%,, -Short 1st metacarpal [HP:0010034],0/22,0%,1/45,2%,, -Short phalanx of the thumb [HP:0009660],0/22,0%,1/45,2%,, Sinus bradycardia [HP:0001688],1/1,100%,2/2,100%,, Abnormal electrophysiology of sinoatrial node origin [HP:0011702],1/1,100%,2/2,100%,, Arrhythmia [HP:0011675],1/1,100%,3/3,100%,, Bradycardia [HP:0001662],1/1,100%,2/2,100%,, -Hypoplasia of deltoid muscle [HP:0030241],0/0,0%,6/6,100%,, -Shoulder muscle hypoplasia [HP:0008952],0/0,0%,6/6,100%,, -Hypoplasia of the musculature [HP:0009004],0/0,0%,6/6,100%,, -Aplasia/Hypoplasia involving the skeletal musculature [HP:0001460],0/0,0%,6/6,100%,, -Abnormality of muscle size [HP:0030236],0/0,0%,6/6,100%,, -Abnormal skeletal muscle morphology [HP:0011805],0/0,0%,8/8,100%,, -Abnormality of the musculature [HP:0003011],0/0,0%,8/8,100%,, -Aplasia/Hypoplasia involving the shoulder musculature [HP:0001464],0/0,0%,6/6,100%,, -Aplasia/Hypoplasia involving the musculature of the upper limbs [HP:0001467],0/0,0%,6/6,100%,, -Aplasia/Hypoplasia involving the musculature of the extremities [HP:0009128],0/0,0%,6/6,100%,, -Abnormality of the musculature of the limbs [HP:0009127],0/0,0%,8/8,100%,, -Abnormality of the musculature of the upper limbs [HP:0001446],0/0,0%,8/8,100%,, -Abnormality of the shoulder girdle musculature [HP:0001435],0/0,0%,6/6,100%,, -Patent foramen ovale [HP:0001655],0/36,0%,4/69,6%,, -Synostosis of joints [HP:0100240],1/1,100%,1/1,100%,, -Abnormality of joint mobility [HP:0011729],5/5,100%,3/3,100%,, -Abnormal joint physiology [HP:0034430],5/5,100%,3/3,100%,, -Abnormal musculoskeletal physiology [HP:0011843],5/5,100%,3/3,100%,, -Abnormality of the vertebral column [HP:0000925],1/1,100%,4/4,100%,, -Upper extremity joint dislocation [HP:0030310],2/2,100%,0/0,0%,, -Joint dislocation [HP:0001373],2/2,100%,0/0,0%,, -Abnormal shoulder morphology [HP:0003043],1/1,100%,1/1,100%,, -Abnormal thorax morphology [HP:0000765],5/5,100%,7/7,100%,, -Limited elbow movement [HP:0002996],4/4,100%,2/2,100%,, -Abnormality of the elbow [HP:0009811],5/5,100%,2/2,100%,, -Limitation of joint mobility [HP:0001376],4/4,100%,2/2,100%,, -Mitral regurgitation [HP:0001653],2/2,100%,2/2,100%,, -Abnormal mitral valve physiology [HP:0031481],2/2,100%,2/2,100%,, -Pre-capillary pulmonary hypertension [HP:0033578],0/0,0%,8/8,100%,, -Elevated pulmonary artery pressure [HP:0004890],0/0,0%,8/8,100%,, -Abnormality of pulmonary circulation [HP:0030875],0/0,0%,8/8,100%,, -Abnormal vascular physiology [HP:0030163],0/0,0%,8/8,100%,, -Abnormal respiratory system physiology [HP:0002795],0/0,0%,8/8,100%,, -Abnormality of the respiratory system [HP:0002086],0/0,0%,8/8,100%,, -Right atrial enlargement [HP:0030718],0/0,0%,4/4,100%,, -Abnormal right atrium morphology [HP:0025580],0/0,0%,4/4,100%,, -Atrial septal dilatation [HP:0011995],0/0,0%,4/4,100%,, Pectus excavatum [HP:0000767],2/2,100%,3/4,75%,, Abnormal sternum morphology [HP:0000766],2/2,100%,3/3,100%,, +Deviation of the thumb [HP:0009603],2/2,100%,3/3,100%,, +Deviation of finger [HP:0004097],2/2,100%,4/4,100%,, +Deviation of the hand or of fingers of the hand [HP:0009484],2/2,100%,5/5,100%,, +Abnormal skin morphology [HP:0011121],1/1,100%,0/0,0%,, +Abnormality of the skin [HP:0000951],1/1,100%,0/0,0%,, +Abnormality of the integument [HP:0001574],1/1,100%,0/0,0%,, +Sinus venosus atrial septal defect [HP:0011567],1/1,100%,0/2,0%,, +First degree atrioventricular block [HP:0011705],1/1,100%,1/23,4%,, Postaxial hand polydactyly [HP:0001162],0/0,0%,3/4,75%,, Postaxial polydactyly [HP:0100259],0/0,0%,3/3,100%,, Polydactyly [HP:0010442],0/0,0%,3/3,100%,, @@ -206,27 +219,22 @@ Enlarged thorax [HP:0100625],0/0,0%,3/3,100%,, Abnormal rib cage morphology [HP:0001547],0/0,0%,5/5,100%,, Y-shaped metatarsals [HP:0010567],0/0,0%,3/3,100%,, Abnormal metatarsal morphology [HP:0001832],0/0,0%,3/3,100%,, -Abnormal lower limb bone morphology [HP:0040069],0/0,0%,4/4,100%,, -Abnormality of the lower limb [HP:0002814],0/0,0%,4/4,100%,, -Abnormal foot morphology [HP:0001760],0/0,0%,4/4,100%,, -Common atrium [HP:0011565],0/38,0%,1/115,1%,, -Unroofed coronary sinus [HP:0031297],0/38,0%,1/117,1%,, -Limited pronation/supination of forearm [HP:0006394],3/3,100%,2/2,100%,, -First degree atrioventricular block [HP:0011705],1/1,100%,1/23,4%,, -Hypoplastic scapulae [HP:0000882],1/1,100%,1/1,100%,, -Aplasia/Hypoplasia of the scapulae [HP:0006713],1/1,100%,1/1,100%,, -Aplasia/Hypoplasia involving bones of the thorax [HP:0006711],2/2,100%,2/2,100%,, -Abnormal scapula morphology [HP:0000782],1/1,100%,1/1,100%,, -Clinodactyly of the 5th finger [HP:0004209],0/0,0%,2/2,100%,, -Finger clinodactyly [HP:0040019],0/0,0%,2/2,100%,, -Clinodactyly [HP:0030084],0/0,0%,2/2,100%,, -Deviation of the 5th finger [HP:0009179],0/0,0%,2/2,100%,, -Abnormal 2nd finger morphology [HP:0004100],0/0,0%,2/2,100%,, +11 pairs of ribs [HP:0000878],0/0,0%,2/2,100%,, +Missing ribs [HP:0000921],0/0,0%,2/2,100%,, +Aplasia/Hypoplasia of the ribs [HP:0006712],0/0,0%,2/2,100%,, +Abnormal rib morphology [HP:0000772],0/0,0%,2/2,100%,, Aplasia/Hypoplasia of the 2nd finger [HP:0006264],0/0,0%,2/2,100%,, -Short middle phalanx of finger [HP:0005819],0/0,0%,2/2,100%,, -Aplasia/Hypoplasia of the middle phalanges of the hand [HP:0009843],0/0,0%,2/2,100%,, -Abnormal middle phalanx morphology of the hand [HP:0009833],0/0,0%,2/2,100%,, -Short phalanx of finger [HP:0009803],0/0,0%,2/2,100%,, +Abnormal 2nd finger morphology [HP:0004100],0/0,0%,2/2,100%,, +Small hypothenar eminence [HP:0010487],0/0,0%,2/2,100%,, +Abnormality of the hypothenar eminence [HP:0010486],0/0,0%,2/2,100%,, +Abnormality of the musculature of the hand [HP:0001421],0/0,0%,2/2,100%,, +Upper extremity joint dislocation [HP:0030310],2/2,100%,0/0,0%,, +Joint dislocation [HP:0001373],2/2,100%,0/0,0%,, +Amelia involving the upper limbs [HP:0009812],1/37,3%,0/114,0%,, +Third degree atrioventricular block [HP:0001709],1/1,100%,0/22,0%,, +Atrioventricular dissociation [HP:0011709],1/1,100%,0/22,0%,, +Abnormal shoulder morphology [HP:0003043],1/1,100%,1/1,100%,, +Proximal placement of thumb [HP:0009623],0/0,0%,3/3,100%,, Short middle phalanx of the 5th finger [HP:0004220],0/0,0%,2/2,100%,, Type A brachydactyly [HP:0009370],0/0,0%,2/2,100%,, Brachydactyly [HP:0001156],0/0,0%,2/2,100%,, @@ -236,27 +244,19 @@ Aplasia/Hypoplasia of the middle phalanx of the 5th finger [HP:0009161],0/0,0%,2 Aplasia/Hypoplasia of the phalanges of the 5th finger [HP:0009376],0/0,0%,2/2,100%,, Abnormal 5th finger phalanx morphology [HP:0004213],0/0,0%,2/2,100%,, Abnormality of the middle phalanx of the 5th finger [HP:0004219],0/0,0%,2/2,100%,, -11 pairs of ribs [HP:0000878],0/0,0%,2/2,100%,, -Missing ribs [HP:0000921],0/0,0%,2/2,100%,, -Aplasia/Hypoplasia of the ribs [HP:0006712],0/0,0%,2/2,100%,, -Abnormal rib morphology [HP:0000772],0/0,0%,2/2,100%,, -Bowed forearm bones [HP:0003956],1/1,100%,0/0,0%,, -Bowing of the arm [HP:0006488],1/1,100%,0/0,0%,, -Bowing of the long bones [HP:0006487],1/1,100%,0/0,0%,, -Abnormal diaphysis morphology [HP:0000940],1/1,100%,0/0,0%,, -Abnormal skin morphology [HP:0011121],1/1,100%,0/0,0%,, -Abnormality of the skin [HP:0000951],1/1,100%,0/0,0%,, -Abnormality of the integument [HP:0001574],1/1,100%,0/0,0%,, -Sinus venosus atrial septal defect [HP:0011567],1/1,100%,0/2,0%,, -Left ventricular noncompaction cardiomyopathy [HP:0011664],1/5,20%,1/7,14%,, -Noncompaction cardiomyopathy [HP:0012817],1/1,100%,1/1,100%,, -Cardiomyopathy [HP:0001638],1/1,100%,1/1,100%,, -Abnormal myocardium morphology [HP:0001637],1/1,100%,1/1,100%,, -Abnormal toe morphology [HP:0001780],0/0,0%,1/1,100%,, -Abnormal toe phalanx morphology [HP:0010161],0/0,0%,1/1,100%,, -Abnormality of the distal phalanges of the toes [HP:0010182],0/0,0%,1/1,100%,, -Amelia involving the upper limbs [HP:0009812],1/37,3%,0/114,0%,, -Third degree atrioventricular block [HP:0001709],1/1,100%,0/22,0%,, -Small hypothenar eminence [HP:0010487],0/0,0%,2/2,100%,, -Abnormality of the hypothenar eminence [HP:0010486],0/0,0%,2/2,100%,, -Abnormality of the musculature of the hand [HP:0001421],0/0,0%,2/2,100%,, +Short middle phalanx of finger [HP:0005819],0/0,0%,2/2,100%,, +Aplasia/Hypoplasia of the middle phalanges of the hand [HP:0009843],0/0,0%,2/2,100%,, +Abnormal middle phalanx morphology of the hand [HP:0009833],0/0,0%,2/2,100%,, +Short phalanx of finger [HP:0009803],0/0,0%,2/2,100%,, +Common atrium [HP:0011565],0/38,0%,1/115,1%,, +Unroofed coronary sinus [HP:0031297],0/38,0%,1/117,1%,, +Clinodactyly of the 5th finger [HP:0004209],0/0,0%,2/2,100%,, +Finger clinodactyly [HP:0040019],0/0,0%,2/2,100%,, +Clinodactyly [HP:0030084],0/0,0%,2/2,100%,, +Deviation of the 5th finger [HP:0009179],0/0,0%,2/2,100%,, +Mitral valve prolapse [HP:0001634],1/1,100%,1/1,100%,, +Abnormal mitral valve morphology [HP:0001633],1/1,100%,1/1,100%,, +Abnormal atrioventricular valve morphology [HP:0006705],1/1,100%,1/1,100%,, +Abnormal heart valve morphology [HP:0001654],1/1,100%,1/1,100%,, +Short 1st metacarpal [HP:0010034],0/22,0%,1/45,2%,, +Short phalanx of the thumb [HP:0009660],0/22,0%,1/45,2%,, diff --git a/docs/user-guide/report/tbx5_frameshift.mtc_report.html b/docs/user-guide/report/tbx5_frameshift.mtc_report.html index 3d00300a0..fbc4a9de4 100644 --- a/docs/user-guide/report/tbx5_frameshift.mtc_report.html +++ b/docs/user-guide/report/tbx5_frameshift.mtc_report.html @@ -103,14 +103,14 @@

Phenotype testing report

 - + - + diff --git a/docs/user-guide/stats.rst b/docs/user-guide/stats.rst index 993dd592e..3eeca2bfc 100644 --- a/docs/user-guide/stats.rst +++ b/docs/user-guide/stats.rst @@ -13,8 +13,6 @@ and explanations of how they are implemented by our software. Compare genotype and phenotype groups ************************************* -TODO - .. _fisher-exact-test: Fisher exact test (FET) @@ -214,7 +212,7 @@ We can now execute the analysis: 17 -Thanks to Phenotype MTC filter, we only tested 16 out of 260 terms. +Thanks to Phenotype MTC filter, we only tested 17 out of 260 terms. We can learn more by showing the MTC filter report: >>> from gpsea.view import MtcStatsViewer diff --git a/src/gpsea/analysis/mtc_filter/_impl.py b/src/gpsea/analysis/mtc_filter/_impl.py index b15e4bc6b..0aca8cc7d 100644 --- a/src/gpsea/analysis/mtc_filter/_impl.py +++ b/src/gpsea/analysis/mtc_filter/_impl.py @@ -181,18 +181,14 @@ class SpecifiedTermsMtcFilter(PhenotypeMtcFilter[hpotk.TermId]): def __init__( self, - hpo: hpotk.MinimalOntology, terms_to_test: typing.Iterable[hpotk.TermId], ): """ - Args: - hpo: reference to HPO ontology object terms_to_test: an iterable of TermIds representing the terms to test """ self._ok = PhenotypeMtcResult.ok() self._fail = PhenotypeMtcResult.fail("Non-specified term") - self._hpo = hpo self._terms_to_test_set = set(terms_to_test) def filter( diff --git a/src/gpsea/analysis/pcats/_impl.py b/src/gpsea/analysis/pcats/_impl.py index 61841a51f..e4513fa0b 100644 --- a/src/gpsea/analysis/pcats/_impl.py +++ b/src/gpsea/analysis/pcats/_impl.py @@ -14,10 +14,16 @@ from gpsea.analysis.pcats.stats import CountStatistic from ..predicate import PatientCategory from ..predicate.genotype import GenotypePolyPredicate -from ..predicate.phenotype import P, PhenotypePolyPredicate, prepare_predicates_for_terms_of_interest +from ..predicate.phenotype import P, PhenotypePolyPredicate from ..mtc_filter import PhenotypeMtcFilter, PhenotypeMtcResult +DEFAULT_MTC_PROCEDURE = 'fdr_bh' +""" +Use Benjamini-Hochberg as the default MTC procedure. +""" + + def apply_predicates_on_patients( patients: typing.Iterable[Patient], gt_predicate: GenotypePolyPredicate, @@ -253,12 +259,23 @@ class MultiPhenotypeAnalysis(typing.Generic[P], metaclass=abc.ABCMeta): def __init__( self, count_statistic: CountStatistic, - mtc_correction: typing.Optional[str] = None, + mtc_correction: typing.Optional[str] = DEFAULT_MTC_PROCEDURE, mtc_alpha: float = 0.05, ): + """ + Create the analysis. + + See the :func:`~statsmodels.stats.multitest.multipletests` for the accepted `mtc_correction` values. + + :param count_statistic: the statistical test for computing p value for genotype-phenotype contingency table. + :param mtc_correction: a `str` with the MTC procedure code or `None` if no MTC should be performed. + :param mtc_alpha: a `float` with the family-wise error rate for FWER controlling procedures + (e.g. Bonferroni MTC) or false discovery rate for the FDR procedures (e.g. Benjamini-Hochberg). + """ assert isinstance(count_statistic, CountStatistic) self._count_statistic = count_statistic self._mtc_correction = mtc_correction + assert isinstance(mtc_alpha, float) and 0. <= mtc_alpha <= 1. self._mtc_alpha = mtc_alpha @abc.abstractmethod @@ -485,7 +502,7 @@ def __init__( self, count_statistic: CountStatistic, mtc_filter: PhenotypeMtcFilter, - mtc_correction: typing.Optional[str] = None, + mtc_correction: typing.Optional[str] = DEFAULT_MTC_PROCEDURE, mtc_alpha: float = 0.05, ): super().__init__( diff --git a/src/gpsea/analysis/pscore/_impl.py b/src/gpsea/analysis/pscore/_impl.py index b2ce8bd24..3d3adbaa5 100644 --- a/src/gpsea/analysis/pscore/_impl.py +++ b/src/gpsea/analysis/pscore/_impl.py @@ -16,29 +16,6 @@ class CountingPhenotypeScorer(PhenotypeScorer): In the case, the query would include the corresponding terms (e.g., Abnormal brain morphology HP:0012443). An individual can then have between 0 and 4 phenotype group abnormalities. This predicate is intended to be used with the Mann Whitney U test. - - Example - ^^^^^^^ - We first need to load HPO using HPO toolkit: - - >>> import hpotk - >>> store = hpotk.configure_ontology_store() - >>> hpo = store.load_minimal_hpo(release='v2024-07-01') - - Now we can create `CountingPhenotypeScorer` to test for presence of brain, liver, kidney and skin abnormalities: - - >>> from gpsea.analysis.pscore import CountingPhenotypeScorer - >>> phenotype_groups = ( - ... "HP:0012443", # Abnormal brain morphology - ... "HP:0410042", # Abnormal liver morphology - ... "HP:0012210", # Abnormal renal morphology - ... "HP:0011121", # Abnormal skin morphology - ... ) - >>> scorer = CountingPhenotypeScorer.from_query_curies( - ... hpo=hpo, - ... query=phenotype_groups, - ... ) - """ @staticmethod diff --git a/tests/analysis/test_mtc_filter.py b/tests/analysis/test_mtc_filter.py index 0b060516f..c07600ef2 100644 --- a/tests/analysis/test_mtc_filter.py +++ b/tests/analysis/test_mtc_filter.py @@ -13,7 +13,7 @@ from gpsea.model import Cohort -class TestHeuristicSamplerMtcFilter: +class TestHpoMtcFilter: @pytest.fixture def mtc_filter( @@ -75,7 +75,7 @@ def test_one_genotype_has_zero_hpo_observations( gt_categories: pd.Index, pheno_categories: pd.Index, ): - counts_df = TestHeuristicSamplerMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) + counts_df = TestHpoMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) actual = HpoMtcFilter.one_genotype_has_zero_hpo_observations( counts=counts_df, @@ -104,7 +104,7 @@ def test_some_cell_has_greater_than_one_count( gt_categories: pd.Index, pheno_categories: pd.Index, ): - counts_df = TestHeuristicSamplerMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) + counts_df = TestHpoMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) actual = HpoMtcFilter.some_cell_has_greater_than_one_count(counts=counts_df) @@ -125,7 +125,7 @@ def test_genotypes_have_same_hpo_proportions( gt_categories: pd.Index, pheno_categories: pd.Index, ): - counts_df = TestHeuristicSamplerMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) + counts_df = TestHpoMtcFilter.prepare_counts_df(counts, gt_categories, pheno_categories) actual = HpoMtcFilter.genotypes_have_same_hpo_proportions( counts=counts_df, @@ -165,7 +165,6 @@ def test_filter_terms_to_test( def test_specified_term_mtc_filter( self, - hpo: hpotk.MinimalOntology, suox_gt_predicate: GenotypePolyPredicate, patient_counts: typing.Tuple[ typing.Mapping[hpotk.TermId, int], @@ -178,7 +177,7 @@ def test_specified_term_mtc_filter( but after our filter, only one survives (filtered_n_usable == 1), and we have four cases in which the reason for filtering out is 'Skipping non-specified term' """ - specified_filter = SpecifiedTermsMtcFilter(hpo=hpo, terms_to_test={hpotk.TermId.from_curie("HP:0032350")}) + specified_filter = SpecifiedTermsMtcFilter(terms_to_test={hpotk.TermId.from_curie("HP:0032350")}) n_usable, all_counts = patient_counts mtc_report = specified_filter.filter_terms_to_test( suox_gt_predicate,
Using HPO MTC filter, 243 term(s) were omitted from statistical analysis.Using HPO MTC filter, 244 term(s) were omitted from statistical analysis.
Code TODO Skipping general term4344
TODO Skipping term with only 2 observations (not powered for 2x2)2526
TODO Skipping term with only 6 observations (not powered for 2x2)1312
TODOSkipping term with maximum frequency that was less than threshold 0.2Skipping term with only 5 observations (not powered for 2x2) 10
TODOSkipping term with only 5 observations (not powered for 2x2)Skipping term with maximum frequency that was less than threshold 0.2 10