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Phenotype Ontology
Like Gene Ontology (GO), phenotypy ontology classifies and organizes gene-mutant/null phenotypic information from the very general at the top to more specific terms in the directed acyclic graph (DAG) by viewing an individual term as a node and its relations to parental terms (allowing for multiple parents) as directed edges. To navigate this hierarchy, we display all parental phenotypic terms to the current phenotypic term of interest ordered by their shortest distances to the current term. Also, only direct children phenotypic terms of the current phenotypic term are listed. Phenotype ontologies we have incorporated are as follows:

• Disease Ontology (DO) Ontology (DO)
  DO semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI thesaurus, SNOMED and OMIM.
  
• Human Phenotype (HP) Ontology (HP)
  HP captures phenotypic abnormalities that are described in OMIM, along with the corresponding disease-causing genes. It includes three complementary biological concepts: Mode_of_Inheritance (MI), ONset_and_clinical_course (ON), and Phenotypic_Abnormality (PA).
  
• Mouse Phenotype (MP) Ontology (MP)
  MP describes phenotypes of the mouse after a specific gene is genetically disrupted. Using it, Mouse Genome Informatics (MGI) provides high-coverate gene-level phenotypes for the mouse.
  
• Worm Phenotype (WP) Ontology (WP)
  WP classifies and organizes phenotype descriptions for C. elegans and other nematodes. Using it, WormBase provides primary resource for phenotype annotations for C. elegans.
  
• Yeast Phenotype (YP) Ontology (YP)
  Based on YP which is the major contributor to the Ascomycete phenotype ontology, Saccharomyces Genome Database (SGD) provides single mutant phenotypes for every gene in the yeast genome.
  
• Fly Phenotype (FP) Ontology (FP)
  FP refers to FlyBase controlled vocabulary. Specifically, a structured controlled vocabulary is used for the annotation of alleles (for their mutagen etc) in FlyBase.
  
• Fly Anatomy (FA) Ontology (FA)
  FA is a structured controlled vocabulary of the anatomy of Drosophila melanogaster, used for the description of phenotypes and where a gene is expressed.
  
• Zebrafish Anatomy (ZA) Ontology (ZA)
  ZA displays anatomical terms of the zebrafish using standard anatomical nomenclature, together with affected genes.
  
• Xenopus Anatomy (XA) Ontology (XA)
  XA represents the lineage of tissues and the timing of development for frogs (Xenopus laevis and Xenopus tropicalis). It is used to annotate Xenopus gene expression patterns and mutant and morphant phenotypes.
  
• Arabidopsis Plant Ontology (AP) Ontology (AP)
  As a major contributor to Plant Ontology which describes plant anatomical and morphological structures (AN) and growth and developmental stages (DE), the Arabidopsis Information Resource (TAIR) provides arabidopsis plant ontology annotations for the model higher plant Arabidopsis thaliana.
  
• Enzyme Commission (EC) Ontology (EC)
  Each enzyme is allocated a four-digit EC number, the first three digits of which define the reaction catalysed and the fourth of which is a unique identifier (serial number). Each enzyme is also assigned a systematic name that uniquely defines the reaction catalysed.
  
• DrugBank ATC (DB) Ontology (DB)
  In the Anatomical Therapeutic Chemical (ATC) classification system, drugs are classified in groups at five different levels according to the organ or system (1st level, anatomical main group) on which they act and their therapeutic (2nd level, therapeutic subgroup), pharmacological (3rd level, pharmacological subgroup) and chemical properties (4th level, chemical subgroup; 5th level, chemical substance). Only drugs in DrugBank are considered.
  
• UniProtKB KeyWords (KW) Ontology (KW)
  Keywords in UniProtKB are controlled vocabulary, providing a summary of the entry content and are used to index UniProtKB/Swiss-Prot entries based on 10 categories (the category "Technical term" being excluded here). Each keyword is attributed manually to UniProtKB/Swiss-Prot entries and automatically to UniProtKB/TrEMBL entries (according to specific annotation rules).
  
• UniProtKB UniPathway (UP) Ontology (UP)
  UP is a fully manually curated resource for the representation and annotation of metabolic pathways, being used as controlled vocabulary for pathway annotation in UniProtKB.
  

Structural Domain Phenotype Ontology and its Annotations
Structural Classification of Proteins (SCOP) classifies evolutionary-related domains into Superfamily level and Family level. Using the phenotype ontologies above, we have generated the domain-centric phenotype annotations, and further identified those phenotype terms which are the most informative to annotate SCOP domains. Promisingly, domain-centric phenotypic annotations can serve as an alternative starting point to explore genotype-phenotype relationships. We provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Structural Domain Disease Ontology (DO) Ontology (SDDO) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DO.txt, and the corresponding ontology:SDDO.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Human Phenotype (HP) Ontology (SDHP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2HP.txt, and the corresponding ontology:SDHP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Mouse Phenotype (MP) Ontology (SDMP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2MP.txt, and the corresponding ontology:SDMP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Worm Phenotype (WP) Ontology (SDWP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2WP.txt, and the corresponding ontology:SDWP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Yeast Phenotype (YP) Ontology (SDYP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2YP.txt, and the corresponding ontology:SDYP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Phenotype (FP) Ontology (SDFP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FP.txt, and the corresponding ontology:SDFP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Fly Anatomy (FA) Ontology (SDFA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2FA.txt, and the corresponding ontology:SDFA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Zebrafish Anatomy (ZA) Ontology (SDZA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2ZA.txt, and the corresponding ontology:SDZA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Xenopus Anatomy (XA) Ontology (SDXA) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2XA.txt, and the corresponding ontology:SDXA.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Arabidopsis Plant Ontology (AP) Ontology (SDAP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2AP.txt, and the corresponding ontology:SDAP.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain Enzyme Commission (EC) Ontology (SDEC) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2EC.txt, and the corresponding ontology:SDEC.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain DrugBank ATC (DB) Ontology (SDDB) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2DB.txt, and the corresponding ontology:SDDB.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB KeyWords (KW) Ontology (SDKW) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2KW.txt, and the corresponding ontology:SDKW.txt) and mysql tables (Domain2PO.sql.gz).
  
• Structural Domain UniProtKB UniPathway (UP) Ontology (SDUP) and its Annotations:
  For details, please visit Document: PO annotation for SCOP domains, wherein Data Availability contains parsable flat files (the annotation:Domain2UP.txt, and the corresponding ontology:SDUP.txt) and mysql tables (Domain2PO.sql.gz).
  

Supra-domain Phenotype Ontology and its Annotations
Although domain-centric annotations hold great promise in describing phenotypic nature of independent domains, most domains themselves may not just work alone. In multi-domain proteins, they may be combined together to form distinct domain architectures. The recombination of the existing domains is considered as one of major driving forces for phenotypic diversificaation. As an extension, we have also generated supra-domain phenotype ontology and its annotations. Compared to domain-centric phenotype ontology and annotations (SCOP domains at the Superfamily level and Family level), this version focuses on supra-domains and individual SCOP domains ONLY at the Superfamily level. Besides, in terms of individual superfamilies, their annotations from the domain-centric version may be different from those from supra-domains version. Depending on your focus, the former should be used for the consideration of both the Superfamily level and Family level, otherwise the latter should be used if you are interested in domain combinations. Also, we provide several relevant files for the download, including the annotation and the corresponding ontology for each phenotype ontology.

• Supra-domain Domain Disease Ontology (DO) Ontology (SPDO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DO.txt, and the corresponding ontology:SPDO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Human Phenotype (HP) Ontology (SPHO) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2HP.txt, and the corresponding ontology:SPHO.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Mouse Phenotype (MP) Ontology (SPMP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2MP.txt, and the corresponding ontology:SPMP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Worm Phenotype (WP) Ontology (SPWP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2WP.txt, and the corresponding ontology:SPWP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Yeast Phenotype (YP) Ontology (SPYP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2YP.txt, and the corresponding ontology:SPYP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Phenotype (FP) Ontology (SPFP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FP.txt, and the corresponding ontology:SPFP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Fly Anatomy (FA) Ontology (SPFA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2FA.txt, and the corresponding ontology:SPFA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Zebrafish Anatomy (ZA) Ontology (SPZA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2ZA.txt, and the corresponding ontology:SPZA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Xenopus Anatomy (XA) Ontology (SPXA) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2XA.txt, and the corresponding ontology:SPXA.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Arabidopsis Plant Ontology (AP) Ontology (SPAP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2AP.txt, and the corresponding ontology:SPAP.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain Enzyme Commission (EC) Ontology (SPEC) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2EC.txt, and the corresponding ontology:SPEC.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain DrugBank ATC (DB) Ontology (SPDB) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2DB.txt, and the corresponding ontology:SPDB.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB KeyWords (KW) Ontology (SPKW) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2KW.txt, and the corresponding ontology:SPKW.txt) and mysql tables (SP2PO.sql.gz).
  
• Supra-domain Domain UniProtKB UniPathway (UP) Ontology (SPUP) and its Annotations:
  For details, please visit Document: PO annotation for Supra-domains, wherein Data Availability contains parsable flat files (the annotation:SP2UP.txt, and the corresponding ontology:SPUP.txt) and mysql tables (SP2PO.sql.gz).
  

Superfamily domains annotated to this XA term (SDXA level: Moderately Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
Guanido kinase N-terminal domain	0	DIRECT
PLP-binding barrel	0	DIRECT
Hedgehog/DD-peptidase	0	DIRECT
Homeodomain-like	0	DIRECT
PriA/YqbF domain	0	DIRECT
14-3-3 protein	0	DIRECT
Synuclein	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Alanine racemase C-terminal domain-like	0	DIRECT
SRF-like	0	DIRECT
"Winged helix" DNA-binding domain	0.000000000000003662	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000000000000004392	DIRECT
RNA-binding domain, RBD	0.0000000003309	DIRECT
Cytokine	0.0000001325	DIRECT
Frizzled cysteine-rich domain	0.0000003656	DIRECT
HMG-box	0.00004549	DIRECT
Cystine-knot cytokines	0.0002027	DIRECT
Sema domain	0.0003469	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.0005736	DIRECT
SAP domain	0.0007387	DIRECT
Snake toxin-like	0.001633	INHERITED FROM: anterior dorsal lateral plate region || ventral mesoderm || dorsal lateral plate mesoderm || involuted dorsal mesoderm || lateral plate mesoderm
Orange domain-like	0.002631	INHERITED FROM: paraxial mesoderm || neurogenic placode || cranial placode
p53-like transcription factors	0.004406	INHERITED FROM: lower blastopore lip || involuted ventral mesoderm || ventral mesoderm || primordium || neurogenic placode || cranial placode
Plexin repeat	0.006891	INHERITED FROM: otic placode || presumptive midbrain-hindbrain boundary || involuted dorsal mesoderm || cranial placode
lambda repressor-like DNA-binding domains	0.01508	INHERITED FROM: presumptive midbrain-hindbrain boundary || neurogenic placode || cranial placode
GroEL-intermediate domain like	0.02065	INHERITED FROM: anterior dorsal lateral plate region
GroEL equatorial domain-like	0.02065	INHERITED FROM: anterior dorsal lateral plate region
GroEL apical domain-like	0.0447	INHERITED FROM: anterior dorsal lateral plate region
beta-beta-alpha zinc fingers	0.09127	INHERITED FROM: presumptive rhombomere || lateral plate mesoderm || splanchnic layer of lateral plate mesoderm
F-box domain	0.1713	INHERITED FROM: optic vesicle
EGF/Laminin	0.1776	INHERITED FROM: axial mesoderm || neural tube || dorsal marginal zone
Transducin (alpha subunit), insertion domain	0.1807	INHERITED FROM: dorsal marginal zone
Alpha-macroglobulin receptor domain	0.1925	INHERITED FROM: foregut || hindgut || midgut
TIMP-like	0.208	INHERITED FROM: axial mesoderm || stomodeal-hypophyseal primordium || prechordal plate
Kazal-type serine protease inhibitors	0.2288	INHERITED FROM: axial mesoderm
FnI-like domain	0.2588	INHERITED FROM: axial mesoderm || prechordal plate || neural tube
Tropomyosin	0.2588	INHERITED FROM: cardiac mesoderm
DNA-binding domain	0.337	INHERITED FROM: eye primordium
Protein kinase-like (PK-like)	0.3744	INHERITED FROM: lateral plate mesoderm
Globin-like	0.4261	INHERITED FROM: anterior dorsal lateral plate region
Terpenoid cyclases/Protein prenyltransferases	0.5167	INHERITED FROM: hindgut || midgut
LDL receptor-like module	0.6314	INHERITED FROM: hindgut
Nuclear receptor ligand-binding domain	0.6418	INHERITED FROM: foregut
E set domains	0.9133	INHERITED FROM: liver diverticulum || liver primordium

Family domains annotated to this XA term (SDXA level: Moderately Informative)
Highlighted in gray are those with FDR_all>0.001

SCOP term	FDR (all)	Annotation (direct or inherited)
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, phosphatase domain	0	DIRECT
Alanine racemase-like, N-terminal domain	0	DIRECT
Troponin I	0	DIRECT
Guanido kinase N-terminal domain	0	DIRECT
Hedgehog (development protein), N-terminal signaling domain	0	DIRECT
Synuclein	0	DIRECT
Ran-binding domain	0	DIRECT
Extracellular domain of cell surface receptors	0	DIRECT
SRF-like	0	DIRECT
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, kinase domain	0	DIRECT
14-3-3 protein	0	DIRECT
SH3BGR (SH3-binding, glutamic acid-rich protein-like)	0	DIRECT
Eukaryotic ODC-like	0	DIRECT
Pointed domain	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Homeodomain	0	DIRECT
Fibroblast growth factors (FGF)	0	DIRECT
Noggin	0	DIRECT
Guanido kinase catalytic domain	0	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.00000000000002443	DIRECT
Forkhead DNA-binding domain	0.0000000000001463	DIRECT
Canonical RBD	0.00000000002004	DIRECT
ets domain	0.0000000179	DIRECT
Transforming growth factor (TGF)-beta	0.0000003984	DIRECT
Frizzled cysteine-rich domain	0.0000005202	DIRECT
HMG-box	0.0000745	DIRECT
Sema domain	0.0001734	DIRECT
POU-specific domain	0.0005725	DIRECT
SAP domain	0.0008643	DIRECT
LIM domain	0.001612	INHERITED FROM: cranial placode
T-box	0.001808	INHERITED FROM: axial mesoderm || lower blastopore lip || involuted ventral mesoderm || involuting marginal zone || cardiac mesoderm || neurogenic placode || circumblastoporal collar || involuted dorsal mesoderm
Hairy Orange domain	0.0027	INHERITED FROM: paraxial mesoderm || neurogenic placode || cranial placode
P4 origin-binding domain-like	0.003989	INHERITED FROM: otic placode || optic vesicle || neurogenic placode || neural tube || cranial placode
Plexin repeat	0.008539	INHERITED FROM: otic placode || presumptive midbrain-hindbrain boundary || cranial placode
Erythroid transcription factor GATA-1	0.0178	INHERITED FROM: liver diverticulum || anterior dorsal lateral plate region || cardiac mesoderm || foregut || primordium || lateral plate mesoderm || cardiac progenitor cell
Actin/HSP70	0.01944	INHERITED FROM: anterior dorsal lateral plate region
VWC domain	0.04226	INHERITED FROM: axial mesoderm || prechordal plate || neural tube
Glutathione peroxidase-like	0.04226	INHERITED FROM: presumptive paraxial mesoderm || paraxial mesoderm || presomitic mesoderm || anterior dorsal lateral plate region || foregut || eye primordium
Paired domain	0.0459	INHERITED FROM: anterior neural tube || primordium || neurogenic placode || neural tube || posterior neural tube || cranial placode
Group II chaperonin (CCT, TRIC), apical domain	0.0459	INHERITED FROM: anterior dorsal lateral plate region || lateral plate mesoderm || upper blastopore lip
Ubiquitin-related	0.06971	INHERITED FROM: upper blastopore lip
Class I aldolase	0.09645	INHERITED FROM: primordium
Group II chaperonin (CCT, TRIC), ATPase domain	0.09645	INHERITED FROM: anterior dorsal lateral plate region
Tandem AAA-ATPase domain	0.0974	INHERITED FROM: blastopore || blastopore lip || marginal zone || upper blastopore lip
Group II chaperonin (CCT, TRIC), intermediate domain	0.09842	INHERITED FROM: anterior dorsal lateral plate region || lateral plate mesoderm
Classic zinc finger, C2H2	0.1391	INHERITED FROM: presumptive rhombomere || lateral plate mesoderm || splanchnic layer of lateral plate mesoderm
Tropomyosin	0.1408	INHERITED FROM: cardiac mesoderm
Transducin (alpha subunit), insertion domain	0.1863	INHERITED FROM: dorsal marginal zone
Alpha-macroglobulin receptor domain	0.19	INHERITED FROM: foregut || hindgut || midgut
F-box domain	0.1966	INHERITED FROM: optic vesicle
AAT-like	0.2508	INHERITED FROM: presomitic mesoderm
Complement components	0.2937	INHERITED FROM: foregut || hindgut || midgut
Link domain	0.4004	INHERITED FROM: presomitic mesoderm
Globins	0.4316	INHERITED FROM: anterior dorsal lateral plate region
Nuclear receptor	0.5043	INHERITED FROM: foregut
LDL receptor-like module	0.6564	INHERITED FROM: hindgut
Nuclear receptor ligand-binding domain	0.6809	INHERITED FROM: foregut
I set domains	0.7993	INHERITED FROM: optic vesicle

Trees by TreeVector

A presence/absence matrix is generated using protein domain architecture data for all genomes in SUPERFAMILY. The PAUP software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Single)	FDR (all)	Annotation (direct or inherited)
Synuclein	0	DIRECT
14-3-3 protein	0	DIRECT
PriA/YqbF domain	0	DIRECT
PLP-binding barrel	0	DIRECT
Guanido kinase N-terminal domain	0	DIRECT
Alanine racemase C-terminal domain-like	0	DIRECT
SRF-like	0	DIRECT
Hedgehog/DD-peptidase	0	DIRECT
Cysteine-rich DNA binding domain, (DM domain)	0	DIRECT
Homeodomain-like	0	DIRECT
"Winged helix" DNA-binding domain	0.000000000000002552	DIRECT
HLH, helix-loop-helix DNA-binding domain	0.000000000000003061	DIRECT
RNA-binding domain, RBD	0.0000000002325	DIRECT
Cytokine	0.00000009405	DIRECT
Frizzled cysteine-rich domain	0.0000002602	DIRECT
HMG-box	0.00003343	DIRECT
Cystine-knot cytokines	0.0001516	DIRECT
Sema domain	0.0002607	DIRECT
Glucocorticoid receptor-like (DNA-binding domain)	0.0004337	DIRECT
SAP domain	0.0005605	DIRECT
Snake toxin-like	0.001251	INHERITED FROM: anterior dorsal lateral plate region || dorsal lateral plate mesoderm || involuted dorsal mesoderm || lateral plate mesoderm || ventral mesoderm
Orange domain-like	0.002032	INHERITED FROM: cranial placode || paraxial mesoderm || neurogenic placode
p53-like transcription factors	0.003422	INHERITED FROM: cranial placode || primordium || lower blastopore lip || involuted ventral mesoderm || neurogenic placode || ventral mesoderm
Plexin repeat	0.005402	INHERITED FROM: cranial placode || involuted dorsal mesoderm || presumptive midbrain-hindbrain boundary || otic placode
Eukaryotic type KH-domain (KH-domain type I)	0.008494	INHERITED FROM: lens placode
lambda repressor-like DNA-binding domains	0.01198	INHERITED FROM: cranial placode || presumptive midbrain-hindbrain boundary || neurogenic placode
GroEL equatorial domain-like	0.01649	INHERITED FROM: anterior dorsal lateral plate region
GroEL-intermediate domain like	0.01649	INHERITED FROM: anterior dorsal lateral plate region
GroEL apical domain-like	0.03651	INHERITED FROM: anterior dorsal lateral plate region
beta-beta-alpha zinc fingers	0.07715	INHERITED FROM: presumptive rhombomere || lateral plate mesoderm || splanchnic layer of lateral plate mesoderm
F-box domain	0.1503	INHERITED FROM: optic vesicle
EGF/Laminin	0.1561	INHERITED FROM: dorsal marginal zone || axial mesoderm || neural tube
Transducin (alpha subunit), insertion domain	0.1589	INHERITED FROM: dorsal marginal zone
Alpha-macroglobulin receptor domain	0.1701	INHERITED FROM: hindgut || foregut || midgut
TIMP-like	0.1847	INHERITED FROM: prechordal plate || axial mesoderm || stomodeal-hypophyseal primordium
Kazal-type serine protease inhibitors	0.2047	INHERITED FROM: axial mesoderm
Tropomyosin	0.2326	INHERITED FROM: cardiac mesoderm
FnI-like domain	0.2326	INHERITED FROM: prechordal plate || axial mesoderm || neural tube
DNA-binding domain	0.3077	INHERITED FROM: eye primordium
Protein kinase-like (PK-like)	0.3441	INHERITED FROM: lateral plate mesoderm
Globin-like	0.3936	INHERITED FROM: anterior dorsal lateral plate region
Terpenoid cyclases/Protein prenyltransferases	0.4825	INHERITED FROM: hindgut || foregut || midgut
LDL receptor-like module	0.597	INHERITED FROM: hindgut
Nuclear receptor ligand-binding domain	0.6075	INHERITED FROM: foregut
E set domains	0.886	INHERITED FROM: liver primordium || liver diverticulum

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Duplex) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
52540,53254 52540 - P-loop containing nucleoside triphosphate hydrolases 53254 - Phosphoglycerate mutase-like	0	DIRECT
53223,51735 53223 - Aminoacid dehydrogenase-like, N-terminal domain 51735 - NAD(P)-binding Rossmann-fold domains	0	DIRECT
47095,47095 47095 - HMG-box 47095 - HMG-box	0	DIRECT
49899,48726 49899 - Concanavalin A-like lectins/glucanases 48726 - Immunoglobulin	0	DIRECT
63501,50242 63501 - Frizzled cysteine-rich domain 50242 - TIMP-like	0	DIRECT
54534,54534 54534 - FKBP-like 54534 - FKBP-like	0	DIRECT
51419,50621 51419 - PLP-binding barrel 50621 - Alanine racemase C-terminal domain-like	0	DIRECT
48034,55931 48034 - Guanido kinase N-terminal domain 55931 - Glutamine synthetase/guanido kinase	0	DIRECT
57716,57716 57716 - Glucocorticoid receptor-like (DNA-binding domain) 57716 - Glucocorticoid receptor-like (DNA-binding domain)	0.0000003178	DIRECT
54928,54928 54928 - RNA-binding domain, RBD 54928 - RNA-binding domain, RBD	0.00003037	DIRECT
101912,103575 101912 - Sema domain 103575 - Plexin repeat	0.0002607	DIRECT
47459,158457 47459 - HLH, helix-loop-helix DNA-binding domain 158457 - Orange domain-like	0.002032	INHERITED FROM: cranial placode || paraxial mesoderm || neurogenic placode
90209,90209 90209 - Ran binding protein zinc finger-like 90209 - Ran binding protein zinc finger-like	0.009559	INHERITED FROM: blastopore || marginal zone || upper blastopore lip || blastopore lip
48592,54849 48592 - GroEL equatorial domain-like 54849 - GroEL-intermediate domain like	0.01452	INHERITED FROM: anterior dorsal lateral plate region
103575,48726 103575 - Plexin repeat 48726 - Immunoglobulin	0.01452	INHERITED FROM: cranial placode
57440,57440 57440 - Kringle-like 57440 - Kringle-like	0.01452	INHERITED FROM: neurogenic placode
47413,46689 47413 - lambda repressor-like DNA-binding domains 46689 - Homeodomain-like	0.01476	INHERITED FROM: cranial placode || presumptive midbrain-hindbrain boundary || neurogenic placode
54849,52029 54849 - GroEL-intermediate domain like 52029 - GroEL apical domain-like	0.0381	INHERITED FROM: anterior dorsal lateral plate region
57196,57196 57196 - EGF/Laminin 57196 - EGF/Laminin	0.05517	INHERITED FROM: dorsal marginal zone
57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.06328	INHERITED FROM: presumptive rhombomere || dorsal lateral plate mesoderm || lateral plate mesoderm || splanchnic layer of lateral plate mesoderm
57196,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.07948	INHERITED FROM: circumblastoporal collar
57850,49599 57850 - RING/U-box 49599 - TRAF domain-like	0.08355	INHERITED FROM: optic vesicle
57716,48508 57716 - Glucocorticoid receptor-like (DNA-binding domain) 48508 - Nuclear receptor ligand-binding domain	0.1266	INHERITED FROM: foregut
52540,52540 52540 - P-loop containing nucleoside triphosphate hydrolases 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1579	INHERITED FROM: blastopore || upper blastopore lip || blastopore lip
47895,52540 47895 - Transducin (alpha subunit), insertion domain 52540 - P-loop containing nucleoside triphosphate hydrolases	0.1589	INHERITED FROM: dorsal marginal zone
46689,46689 46689 - Homeodomain-like 46689 - Homeodomain-like	0.2186	INHERITED FROM: optic vesicle
55550,56112 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0.2403	INHERITED FROM: non-involuting marginal zone
49854,49854 49854 - Spermadhesin, CUB domain 49854 - Spermadhesin, CUB domain	0.2818	INHERITED FROM: primordium
57184,57184 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0.4091	INHERITED FROM: presomitic mesoderm || dorsal marginal zone
50044,55550 50044 - SH3-domain 55550 - SH2 domain	0.6222	INHERITED FROM: non-involuting marginal zone

Supra-domains annotated to this XA term (SPXA level: Moderately Informative)
Highlighted in gray are those with FDR>0.001

Supra-domain (Triple) in N- to C-terminal order	FDR (all)	Annotation (direct or inherited)
57196,49854,57196 57196 - EGF/Laminin 49854 - Spermadhesin, CUB domain 57196 - EGF/Laminin	0	DIRECT
103647,103647,103647 103647 - TSP type-3 repeat 103647 - TSP type-3 repeat 103647 - TSP type-3 repeat	0	DIRECT
49899,48726,49265 49899 - Concanavalin A-like lectins/glucanases 48726 - Immunoglobulin 49265 - Fibronectin type III	0	DIRECT
47220,47220,47220 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like 47220 - alpha-catenin/vinculin-like	0	DIRECT
49854,49854,57196 49854 - Spermadhesin, CUB domain 49854 - Spermadhesin, CUB domain 57196 - EGF/Laminin	0	DIRECT
57603,57603,57603 57603 - FnI-like domain 57603 - FnI-like domain 57603 - FnI-like domain	0.003176	INHERITED FROM: circumblastoporal collar
48592,54849,52029 48592 - GroEL equatorial domain-like 54849 - GroEL-intermediate domain like 52029 - GroEL apical domain-like	0.01452	INHERITED FROM: anterior dorsal lateral plate region
101912,103575,48726 101912 - Sema domain 103575 - Plexin repeat 48726 - Immunoglobulin	0.01452	INHERITED FROM: cranial placode
57196,57196,57184 57196 - EGF/Laminin 57196 - EGF/Laminin 57184 - Growth factor receptor domain	0.03651	INHERITED FROM: presomitic mesoderm || dorsal marginal zone
50044,55550,56112 50044 - SH3-domain 55550 - SH2 domain 56112 - Protein kinase-like (PK-like)	0.03651	INHERITED FROM: non-involuting marginal zone
48726,49265,49265 48726 - Immunoglobulin 49265 - Fibronectin type III 49265 - Fibronectin type III	0.08355	INHERITED FROM: optic vesicle
57196,57184,57184 57196 - EGF/Laminin 57184 - Growth factor receptor domain 57184 - Growth factor receptor domain	0.08699	INHERITED FROM: presomitic mesoderm || dorsal marginal zone || neural tube || paraxial mesoderm
57667,57667,57667 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers 57667 - beta-beta-alpha zinc fingers	0.9999	INHERITED FROM: splanchnic layer of lateral plate mesoderm

Trees by TreeVector

A presence/absence matrix is generated using protein domains and supradomains for all genomes in SUPERFAMILY. The RAxML software is used to produce a single, large tree topology using heuristic parsimony methods. Genome combinations, or specific clades, can be displayed as if individual trees had been produced. However, this data is extracted from the single large tree. This produces a higher quality topology than if the trees had been produced on their own, and allows the trees to be displayed instantly.