View original ARBA rule on UniProt
Rule predicts sexual sporulation resulting in cellular spore formation based on 5 condition sets containing diverse protein families (kinases, trafficking proteins, cell wall enzymes, motor proteins) across eukaryotic taxa
Condition-set counts describe the sets recorded in this review, which may omit the full rule.
Interactive prediction matrix showing how row entries PREDICT column entries. Cell (i,j) shows what fraction of proteins with row domain i also have column domain j. Click cells to view intersection in UniProt. Click domain IDs to view proteins with that domain.
Legend: Each cell shows PREDICTS % (fraction of row entry proteins that also have column entry - row PREDICTS column), Jaccard similarity (J:%), and intersection count. CS = Condition Set(s), TGT = GO annotation target.
ARBA00086620 demonstrates critical design flaws that render it unsuitable for accurate GO annotation. The rule combines functionally diverse protein families (MAPK, 14-3-3, syntaxins, chitin deacetylases, dynein light chains) that lack mechanistic coherence for sexual sporulation. The taxonomic scope is inappropriate, applying fungal-specific processes to all eukaryotes. Most concerning, the rule currently matches 0 proteins, indicating unrealistic condition combinations. The low domain overlap (avg Jaccard=0.006) confirms that these condition sets identify completely different protein populations. This rule represents a clear case of over-annotation risk and should be deprecated to prevent false positive GO assignments.
This rule should be deprecated due to fundamental design flaws: (1) Mechanistic incoherence - combining unrelated protein families (kinases, trafficking proteins, cell wall enzymes, motor proteins) that do not share a common role in sexual sporulation; (2) Taxonomic over-annotation - applying fungal-specific sexual sporulation processes to all eukaryotes where such mechanisms may not exist; (3) Poor biological validation - 0 protein matches indicate unrealistic condition combinations; (4) High false positive risk - the diverse protein families could match proteins involved in other cellular processes unrelated to sporulation. The rule fails basic biological plausibility tests and would likely produce more annotation errors than correct predictions.
| Condition A | Condition B | Count A | Count B | Intersection | Jaccard | A in B | B in A | Interpretation |
|---|---|---|---|---|---|---|---|---|
1.10.510.10:FF:000624
|
3.30.200.20:FF:001493
|
25 | 2 | 2 | 0.080 | 0.080 | 1.000 | SUBSET |
Rule contains 5 condition sets with functionally diverse protein families that lack biological coherence. The sporulation protein kinase domain is completely contained within the MAPK family (containment=1.0), indicating redundancy. Most condition sets are completely disjoint (Jaccard=0.0), suggesting they identify unrelated protein populations rather than coherent functional modules for sexual sporulation.
While individual proteins may have roles in cellular processes, there is no literature support for the broad claim that MAPK+14-3-3+syntaxins+chitin deacetylases+dynein light chains collectively predict sexual sporulation. Sexual sporulation is a complex process primarily studied in fungi, involving meiosis, spore wall formation, and specialized cellular reorganization. The rule inclusion of diverse protein families without mechanistic connection contradicts established understanding of sporulation biology.
Quantitative analysis reveals minimal overlap between condition sets (average Jaccard similarity = 0.006). Most condition pairs are completely disjoint (Jaccard = 0.0), indicating they identify entirely different protein populations. The only significant relationship is the complete containment of sporulation kinase proteins within the MAPK family. This pattern suggests the conditions capture unrelated biological processes rather than coherent functional modules for sexual sporulation.
GO:0043935 "sexual sporulation resulting in formation of a cellular spore" is a highly specific biological process primarily observed in fungi and some protists. The rule conditions (MAPK, 14-3-3, syntaxins, chitin deacetylases, dynein light chains) represent diverse molecular functions that do not specifically predict this process. The term specificity is appropriate, but the protein families selected do not provide reliable predictive power for sexual sporulation.
Condition set 1 applies to all Eukaryota, which is inappropriate for sexual sporulation mechanisms that are not universally conserved. Sexual sporulation is primarily a fungal process with some occurrence in protists, but the molecular mechanisms and regulatory pathways vary significantly across eukaryotic lineages. The rule incorrectly assumes that the presence of MAPK+sporulation kinase domains predicts sexual sporulation across all eukaryotes, which would lead to massive over-annotation in lineages where this process does not occur.
Rule contains 5 functionally diverse protein families that lack mechanistic coherence for sexual sporulation
Taxonomic scope inappropriately applies fungal-specific processes to all eukaryotes
Zero protein matches suggest unrealistic condition combinations
Average Jaccard similarity of 0.006 indicates completely disjoint condition sets
Most condition pairs show 0% protein overlap (disjoint relationships)
Sporulation protein kinase completely contained within MAPK family (containment=1.0)
Very low GO term coverage across all conditions
id: ARBA00086620
description: 'Rule predicts sexual sporulation resulting in cellular spore formation based on 5 condition sets containing diverse protein families (kinases, trafficking proteins, cell wall enzymes, motor proteins) across eukaryotic taxa'
status: COMPLETE
rule_type: ARBA
rule:
rule_id: ARBA00086620
condition_sets:
- number: 1
conditions:
- condition_type: FUNFAM
value: 1.10.510.10:FF:000624
curie: CATH.FunFam:1.10.510.10:FF:000624
label: Mitogen-activated protein kinase
negated: false
- condition_type: FUNFAM
value: 3.30.200.20:FF:001493
curie: CATH.FunFam:3.30.200.20:FF:001493
label: Sporulation protein kinase mde3
negated: false
- condition_type: TAXON
value: Eukaryota
curie: NCBITaxon:2759
label: Eukaryota
negated: false
notes: ''
pairwise_overlap:
- condition_a: 1.10.510.10:FF:000624
condition_b: 3.30.200.20:FF:001493
protein_database: SWISSPROT
count_a: 25
count_b: 2
intersection_count: 2
a_minus_b_count: 23
b_minus_a_count: 0
jaccard_similarity: 0.08
containment_a_in_b: 0.08
containment_b_in_a: 1.0
interpretation: SUBSET
- number: 2
conditions:
- condition_type: FUNFAM
value: 1.20.190.20:FF:000002
curie: CATH.FunFam:1.20.190.20:FF:000002
label: 14-3-3 protein epsilon
negated: false
- condition_type: TAXON
value: Saccharomycetes
curie: NCBITaxon:4891
label: Saccharomycetes
negated: false
notes: ''
- number: 3
conditions:
- condition_type: FUNFAM
value: 1.20.58.70:FF:000008
curie: CATH.FunFam:1.20.58.70:FF:000008
label: Syntaxin family protein
negated: false
- condition_type: TAXON
value: Saccharomycetales
curie: NCBITaxon:4892
label: Saccharomycetales
negated: false
notes: ''
- number: 4
conditions:
- condition_type: FUNFAM
value: 3.20.20.370:FF:000008
curie: CATH.FunFam:3.20.20.370:FF:000008
label: Chitin deacetylase
negated: false
- condition_type: TAXON
value: Fungi
curie: NCBITaxon:4751
label: Fungi
negated: false
notes: ''
- number: 5
conditions:
- condition_type: FUNFAM
value: 3.30.740.10:FF:000001
curie: CATH.FunFam:3.30.740.10:FF:000001
label: Dynein light chain
negated: false
- condition_type: TAXON
value: Dikarya
curie: NCBITaxon:451864
label: Dikarya
negated: false
notes: ''
go_annotations: []
reviewed_protein_count: 0
unreviewed_protein_count: 0
created_date: ''
modified_date: ''
entries:
- id: 1.10.510.10:FF:000624
type: FUNFAM
label: Mitogen-activated protein kinase
appears_in_condition_sets:
- 1
protein_count: 25
related_entries:
- relationship: PREDICTED_BY
target_id: 3.30.200.20:FF:001493
containment: 1.0
jaccard_similarity: 0.08
intersection_count: 2
exclusive_count: 0
- relationship: EQUIV
target_id: 1.20.190.20:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 25
- relationship: EQUIV
target_id: 1.20.58.70:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 25
- relationship: EQUIV
target_id: 3.20.20.370:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 25
- relationship: EQUIV
target_id: 3.30.740.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 25
- relationship: PREDICTS
target_id: GO:0043935
containment: 0.08
jaccard_similarity: 0.007
intersection_count: 2
exclusive_count: 23
- id: 1.20.190.20:FF:000002
type: FUNFAM
label: 14-3-3 protein epsilon
appears_in_condition_sets:
- 2
protein_count: 69
related_entries:
- relationship: EQUIV
target_id: 1.10.510.10:FF:000624
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 69
- relationship: EQUIV
target_id: 3.30.200.20:FF:001493
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 69
- relationship: EQUIV
target_id: 1.20.58.70:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 69
- relationship: EQUIV
target_id: 3.20.20.370:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 69
- relationship: EQUIV
target_id: 3.30.740.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 69
- relationship: EQUIV
target_id: GO:0043935
containment: 0.029
jaccard_similarity: 0.006
intersection_count: 2
exclusive_count: 67
- id: 1.20.58.70:FF:000008
type: FUNFAM
label: Syntaxin family protein
appears_in_condition_sets:
- 3
protein_count: 4
related_entries:
- relationship: EQUIV
target_id: 1.10.510.10:FF:000624
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.30.200.20:FF:001493
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 1.20.190.20:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.20.20.370:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: EQUIV
target_id: 3.30.740.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 4
- relationship: PREDICTS
target_id: GO:0043935
containment: 0.75
jaccard_similarity: 0.011
intersection_count: 3
exclusive_count: 1
- id: 3.20.20.370:FF:000008
type: FUNFAM
label: Chitin deacetylase
appears_in_condition_sets:
- 4
protein_count: 2
related_entries:
- relationship: EQUIV
target_id: 1.10.510.10:FF:000624
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.30.200.20:FF:001493
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 1.20.190.20:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 1.20.58.70:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.30.740.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: PREDICTS
target_id: GO:0043935
containment: 1.0
jaccard_similarity: 0.008
intersection_count: 2
exclusive_count: 0
- id: 3.30.200.20:FF:001493
type: FUNFAM
label: Sporulation protein kinase mde3
appears_in_condition_sets:
- 1
protein_count: 2
related_entries:
- relationship: PREDICTS
target_id: 1.10.510.10:FF:000624
containment: 0.08
jaccard_similarity: 0.08
intersection_count: 2
exclusive_count: 23
- relationship: EQUIV
target_id: 1.20.190.20:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 1.20.58.70:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.20.20.370:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: EQUIV
target_id: 3.30.740.10:FF:000001
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 2
- relationship: PREDICTS
target_id: GO:0043935
containment: 1.0
jaccard_similarity: 0.008
intersection_count: 2
exclusive_count: 0
- id: 3.30.740.10:FF:000001
type: FUNFAM
label: Dynein light chain
appears_in_condition_sets:
- 5
protein_count: 20
related_entries:
- relationship: EQUIV
target_id: 1.10.510.10:FF:000624
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 20
- relationship: EQUIV
target_id: 3.30.200.20:FF:001493
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 20
- relationship: EQUIV
target_id: 1.20.190.20:FF:000002
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 20
- relationship: EQUIV
target_id: 1.20.58.70:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 20
- relationship: EQUIV
target_id: 3.20.20.370:FF:000008
containment: 0.0
jaccard_similarity: 0.0
intersection_count: 0
exclusive_count: 20
- relationship: PREDICTS
target_id: GO:0043935
containment: 0.1
jaccard_similarity: 0.007
intersection_count: 2
exclusive_count: 18
review_summary: 'ARBA00086620 demonstrates critical design flaws that render it unsuitable for accurate GO annotation. The rule combines functionally diverse protein families (MAPK, 14-3-3, syntaxins, chitin deacetylases, dynein light chains) that lack mechanistic coherence for sexual sporulation. The taxonomic scope is inappropriate, applying fungal-specific processes to all eukaryotes. Most concerning, the rule currently matches 0 proteins, indicating unrealistic condition combinations. The low domain overlap (avg Jaccard=0.006) confirms that these condition sets identify completely different protein populations. This rule represents a clear case of over-annotation risk and should be deprecated to prevent false positive GO assignments.'
action: DEPRECATE
action_rationale: 'This rule should be deprecated due to fundamental design flaws: (1) Mechanistic incoherence - combining unrelated protein families (kinases, trafficking proteins, cell wall enzymes, motor proteins) that do not share a common role in sexual sporulation; (2) Taxonomic over-annotation - applying fungal-specific sexual sporulation processes to all eukaryotes where such mechanisms may not exist; (3) Poor biological validation - 0 protein matches indicate unrealistic condition combinations; (4) High false positive risk - the diverse protein families could match proteins involved in other cellular processes unrelated to sporulation. The rule fails basic biological plausibility tests and would likely produce more annotation errors than correct predictions.'
suggested_modifications: []
parsimony:
assessment: OVERLY_COMPLEX
notes: 'Rule contains 5 condition sets with functionally diverse protein families that lack biological coherence. The sporulation protein kinase domain is completely contained within the MAPK family (containment=1.0), indicating redundancy. Most condition sets are completely disjoint (Jaccard=0.0), suggesting they identify unrelated protein populations rather than coherent functional modules for sexual sporulation.'
literature_support:
assessment: CONTRADICTED
notes: 'While individual proteins may have roles in cellular processes, there is no literature support for the broad claim that MAPK+14-3-3+syntaxins+chitin deacetylases+dynein light chains collectively predict sexual sporulation. Sexual sporulation is a complex process primarily studied in fungi, involving meiosis, spore wall formation, and specialized cellular reorganization. The rule inclusion of diverse protein families without mechanistic connection contradicts established understanding of sporulation biology.'
supported_by:
- reference_id: file:rules/arba/ARBA00086620/ARBA00086620-deep-research-manual.md
supporting_text: 'Sexual sporulation in eukaryotes, particularly fungi, involves: Cell cycle regulation and meiosis, Spore wall synthesis and modification, Membrane fusion and trafficking, Cytoskeletal reorganization. While some rule components may participate in these processes, the broad inclusion of diverse protein families without clear mechanistic connection is problematic.'
condition_overlap:
assessment: NONE
notes: 'Quantitative analysis reveals minimal overlap between condition sets (average Jaccard similarity = 0.006). Most condition pairs are completely disjoint (Jaccard = 0.0), indicating they identify entirely different protein populations. The only significant relationship is the complete containment of sporulation kinase proteins within the MAPK family. This pattern suggests the conditions capture unrelated biological processes rather than coherent functional modules for sexual sporulation.'
supported_by:
- reference_id: file:rules/arba/ARBA00086620/ARBA00086620-analysis.yaml
supporting_text: 'Summary: Analyzed 15 domain-domain pairs and 6 domain-GO pairs across entire rule. Average Jaccard similarity: 0.006. 0 pairs with >50% overlap, 3 subset relationships.'
go_specificity:
assessment: MISMATCHED
notes: 'GO:0043935 "sexual sporulation resulting in formation of a cellular spore" is a highly specific biological process primarily observed in fungi and some protists. The rule conditions (MAPK, 14-3-3, syntaxins, chitin deacetylases, dynein light chains) represent diverse molecular functions that do not specifically predict this process. The term specificity is appropriate, but the protein families selected do not provide reliable predictive power for sexual sporulation.'
supported_by: []
taxonomic_scope:
assessment: TOO_BROAD
notes: 'Condition set 1 applies to all Eukaryota, which is inappropriate for sexual sporulation mechanisms that are not universally conserved. Sexual sporulation is primarily a fungal process with some occurrence in protists, but the molecular mechanisms and regulatory pathways vary significantly across eukaryotic lineages. The rule incorrectly assumes that the presence of MAPK+sporulation kinase domains predicts sexual sporulation across all eukaryotes, which would lead to massive over-annotation in lineages where this process does not occur.'
supported_by:
- reference_id: file:rules/arba/ARBA00086620/ARBA00086620-deep-research-manual.md
supporting_text: 'Sexual sporulation mechanisms vary significantly across eukaryotic kingdoms. GO:0043935 "sexual sporulation resulting in formation of a cellular spore" is a very specific biological process primarily observed in: Fungi (especially yeasts and filamentous fungi), Some protists, Not universally present across all eukaryotes.'
confidence: 0.9
references:
- id: file:rules/arba/ARBA00086620/ARBA00086620-deep-research-manual.md
title: Manual deep research analysis
findings:
- statement: 'Rule contains 5 functionally diverse protein families that lack mechanistic coherence for sexual sporulation'
- statement: 'Taxonomic scope inappropriately applies fungal-specific processes to all eukaryotes'
- statement: 'Zero protein matches suggest unrealistic condition combinations'
- statement: 'Average Jaccard similarity of 0.006 indicates completely disjoint condition sets'
- id: file:rules/arba/ARBA00086620/ARBA00086620-analysis.yaml
title: Quantitative domain overlap analysis
findings:
- statement: 'Most condition pairs show 0% protein overlap (disjoint relationships)'
- statement: 'Sporulation protein kinase completely contained within MAPK family (containment=1.0)'
- statement: 'Very low GO term coverage across all conditions'
supported_by:
- reference_id: file:rules/arba/ARBA00086620/ARBA00086620-deep-research-manual.md
supporting_text: 'This rule appears to suffer from significant design flaws that make it unsuitable for accurate GO annotation: 1. Overly broad taxonomic scope - sexual sporulation mechanisms are not conserved across all eukaryotes; 2. Mechanistic incoherence - mixing proteins from unrelated functional categories; 3. Poor biological validation - no protein matches suggest unrealistic conditions'