Surveillance Immunity Gene Curation: Implementation Checklist

MATURE BIOLOGY_DOMAIN

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Surveillance Immunity Gene Curation: Implementation Checklist

Overview

This document provides a line-by-line implementation checklist for updating the 6 surveillance immunity gene reviews based on the comprehensive curation summary.

Target genes: daf-16, dbl-1, sta-2, nipi-3, lys-7, clec-60
Total annotations to review: 238
Estimated effort: 40-60 hours for complete implementation

CLEC-60 (Q23564) - START HERE (SIMPLEST, 1 annotation + 3 NEW)

Existing Annotations in GOA

Row 2: GO:0050830 | defense response to Gram-positive bacterium | IGI | PMID:20617181

Actions Required

Annotation 1: GO:0050830 (defense response to Gram-positive bacterium)
- [ ] Status: ACCEPT (no changes needed)
- [ ] Verify PMID:20617181 is available in publications/ directory
- [ ] Confirm that Q23565 (clec-61) is correctly cited as With/From gene
- [ ] Ensure supporting text in review file includes: "clec-60 upregulation 8.3-fold during S. aureus infection"

NEW Annotation 1: GO:0030246 (carbohydrate binding)
- [ ] Action: ADD
- [ ] Evidence type: IEA
- [ ] Reference: GO_REF:0000002 (InterPro domain mapping)
- [ ] Supporting text: "C-type lectin domain (IPR001304) is characterized by calcium-dependent carbohydrate-binding activity"
- [ ] Summary: CLEC-60 contains C-type lectin-like domain enabling carbohydrate recognition
- [ ] Reason: Domain composition supports carbohydrate binding function consistent with pathogen recognition

NEW Annotation 2: GO:0140367 (antibacterial innate immune response)
- [ ] Action: ADD
- [ ] Evidence type: IMP
- [ ] Reference: PMID:20617181
- [ ] Supporting text: "Transgenic animals carrying clec-60,61 cluster extrachromosomal arrays survived longer (LT50 = 54.2 h) during S. aureus infection"
- [ ] Summary: CLEC-60 functions as an effector in innate immune response to bacterial infection
- [ ] Reason: Overexpression provides protection during S. aureus infection demonstrating functional role

NEW Annotation 3: GO:0005576 (extracellular region)
- [ ] Action: ADD
- [ ] Evidence type: IEA
- [ ] Reference: GO_REF:0000002 (SignalP prediction)
- [ ] Supporting text: "Signal peptide (residues 1-17) indicating secretion to extracellular space"
- [ ] Summary: CLEC-60 is secreted via N-terminal signal peptide
- [ ] Reason: Signal peptide consistent with role as secreted antimicrobial effector

Checklist for CLEC-60

LYS-7 (O16202) - 18 annotations (Priority: HIGH - has critical errors)

Critical Issues to Address

ISSUE 1: Row 2 - GO:0007165 (signal transduction) - IBA
- [ ] Action: REMOVE
- [ ] Reason: LYS-7 is an effector downstream of signaling pathways, not a signaling component itself
- [ ] Supported by: PMID:18927620 "repression of immune effector expression, such as...lys-7, may represent a virulence mechanism"
- [ ] Remove this line from review: "involved_in: GO:0007165"

ISSUE 2: Row 5 - GO:0003796 (lysozyme activity) - IEA via InterPro
- [ ] Action: REMOVE (or MODIFY with caveat)
- [ ] Reason: LYS-7 lacks conserved catalytic residues; is a pseudolysozyme
- [ ] Check UniProt record for mention of catalytic residue absence
- [ ] If must keep: Add annotation note "catalytically inactive pseudolysozyme"
- [ ] Recommend removal entirely

ISSUE 3: Row 7 - GO:0009253 (peptidoglycan catabolic process) - IEA
- [ ] Action: REMOVE
- [ ] Reason: Infers enzymatic activity that LYS-7 doesn't possess
- [ ] Supporting evidence: Lacks key catalytic residues for peptidoglycan cleavage
- [ ] Remove this annotation

ISSUE 4: Row 8 - GO:0016998 (cell wall macromolecule catabolic process) - IEA
- [ ] Action: REMOVE
- [ ] Reason: Same issue as above - non-catalytic protein
- [ ] Remove this annotation

Annotations to ACCEPT

Row 3: GO:0045087 (innate immune response) - IBA
- [ ] Status: ACCEPT
- [ ] Keep as is
- [ ] Note: Phylogenetic inference supported by extensive IMP evidence below

Row 9: GO:0045087 (innate immune response) - IEA via UniProt-KW
- [ ] Status: CONSOLIDATE or REMOVE duplicate
- [ ] Option 1: Remove this entry (redundant with row 3 IBA)
- [ ] Option 2: Keep and mark as secondary evidence if IBA unavailable

Rows 10-12: GO:0050830 (defense response to Gram-positive bacterium) - IMP
- [ ] Status: ACCEPT (keep all 3 entries - multiple studies)
- [ ] PMID:16809667, PMID:22841995 (appears twice)
- [ ] Verify citations exist in publications/ directory

Row 13: GO:0050832 (defense response to fungus) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:21399680
- [ ] Verify evidence of C. neoformans protection

Rows 14-18: GO:0050829 (defense response to Gram-negative bacterium) - IMP/IGI
- [ ] Status: ACCEPT (most entries)
- [ ] Row 14: PMID:18927620 (IMP) - ACCEPT
- [ ] Row 18: PMID:21399680 (IGI with WB:WBGene00000018) - ACCEPT
- [ ] Note duplicates if present

Row 16: GO:0045087 (innate immune response) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:19023415
- [ ] Strongest evidence (IMP with manipulation)

Checklist for LYS-7

NIPI-3 (G5EED4) - 18 annotations (Priority: HIGH - pseudokinase issue)

Critical Issues to Address

ISSUE 1: Row 6 - GO:0004672 (protein kinase activity) - IEA
- [ ] Action: REMOVE
- [ ] Reason: NIPI-3 is a pseudokinase; lacks catalytic residues; NOT a functional kinase
- [ ] Explanation: Domain similarity to kinases should not infer catalytic activity for pseudokinases
- [ ] Remove this annotation

ISSUE 2: Row 7 - GO:0005524 (ATP binding) - IEA
- [ ] Action: MODIFY or KEEP with caveat
- [ ] Reason: NIPI-3 contains ATP-binding pocket in kinase domain but kinase is inactive
- [ ] Option 1: Keep with annotation note "catalytically inactive pseudokinase; ATP binding predicted but functional relevance unclear"
- [ ] Option 2: Remove if no experimental evidence of ATP binding
- [ ] Recommendation: MODIFY to keep but flag as non-functional

ISSUE 3: Row 4 - GO:0032436 (positive regulation of proteasomal ubiquitin-dependent protein catabolic process) - IBA
- [ ] Action: KEEP_AS_NON_CORE (not REMOVE)
- [ ] Reason: Mammalian Tribbles promote C/EBP degradation, but C. elegans NIPI-3 regulates CEBP-1 transcriptionally
- [ ] Supporting evidence: PMID:27927209 shows translational reporter no differences in nipi-3 mutants
- [ ] Action: Mark as non-core function or secondary mechanism

Annotations to ACCEPT

Row 2: GO:0005634 (nucleus) is_active_in - IBA
- [ ] Status: ACCEPT
- [ ] Supporting evidence: PMID:27927209 GFP localization shows nuclear predominance
- [ ] Keep as is

Row 3: GO:0031434 (mitogen-activated protein kinase kinase binding) - IBA
- [ ] Status: ACCEPT
- [ ] Phylogenetically reasonable and functionally supported by sek-1 genetic interaction
- [ ] Keep as is

Row 5: GO:0000166 (nucleotide binding) - IEA
- [ ] Status: KEEP with caveat
- [ ] Action: Add annotation note: "Predicted nucleotide binding in pseudokinase domain; functional relevance unclear"
- [ ] Keep but flag

Rows 9-12: Immune Response Annotations (GO:0010468, GO:0010629, GO:0050829, GO:0050830)
- [ ] All STATUS: ACCEPT
- [ ] These are core NIPI-3 functions with solid IMP evidence
- [ ] PMID:27927200 (rows 9, 11)
- [ ] PMID:34407394 (rows 10, 12)
- [ ] Keep all entries

Rows 13-18: Additional Immune Annotations
- [ ] Row 13: GO:0010629 (negative regulation of gene expression) - ACCEPT
- [ ] Row 14: GO:0140297 (DNA-binding transcription factor binding) - ACCEPT (CEBP-1 interaction)
- [ ] Row 15: GO:0010628 (positive regulation of gene expression) - ACCEPT
- [ ] Rows 16-18: GO:0050832 (defense response to fungus) - ACCEPT both entries

Checklist for NIPI-3

STA-2 (Q20977) - 27 annotations (Priority: MEDIUM)

Complex Annotations Requiring Review

ISSUE 1: Row 8 - GO:0007259 (cell surface receptor signaling pathway via JAK-STAT) - IBA
- [ ] Action: MODIFY or ADD_CAVEAT
- [ ] Problem: C. elegans lacks JAK kinases; sta-2 activated through SNF-12 transporter instead
- [ ] Recommendation: Keep annotation but add note that activation mechanism differs from JAK-STAT
- [ ] Supporting evidence: PMID:21575913, PMID:25692704
- [ ] Modify summary: "STA-2 functions similarly to mammalian STATs but through JAK-independent mechanism via SNF-12 transporter"

ISSUE 2: Row 4 - GO:0042127 (regulation of cell population proliferation) - IBA
- [ ] Action: KEEP_AS_NON_CORE
- [ ] Reason: Phylogenetically inferred from mammalian STATs but no C. elegans evidence for sta-2 role in proliferation
- [ ] Keep but mark as secondary, not core to surveillance immunity

ISSUE 3: Redundant DNA Binding Annotations (Rows 6, 10, 11, 42)
- [ ] Row 6: GO:0000978 (RNA pol II cis-regulatory region binding) IBA - KEEP PRIMARY
- [ ] Row 10: GO:0003677 (DNA binding) IEA - REMOVE or mark redundant
- [ ] Row 11: GO:0003700 (DNA-binding transcription factor activity) IEA - KEEP but secondary
- [ ] Row 42: GO:0000978 IDA - ADD if not already present
- [ ] Consolidate: Keep rows 6 and 11; remove row 10 as too generic

Annotations to ACCEPT (Core Immune Functions)

Row 21: GO:0050832 (defense response to fungus) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:22470487
- [ ] Core immune function

Row 28: GO:0002804 (positive regulation of antifungal peptide production) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:21575913
- [ ] PRIMARY functional output of sta-2
- [ ] This is the most important annotation for surveillance immunity

Row 19: GO:0009611 (response to wounding) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:22470487
- [ ] Part of epidermal damage response

Row 20: GO:0010628 (positive regulation of gene expression) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:22470487
- [ ] Mechanistic description of AMP induction

Row 3: GO:0006952 (defense response) - IBA
- [ ] Status: ACCEPT
- [ ] Broad term supported by specific immune annotations below

Rows 2, 5, 9: Localization/Activity (nucleus, TF activity)
- [ ] All STATUS: ACCEPT
- [ ] IBA annotations phylogenetically appropriate
- [ ] Supported by IDA evidence in PMID:21575913, PMID:31735670

Structural Annotations (Hemidesmosome - Non-core but keep)

Rows 23-24: Hemidesmosome localization
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Mechanistically interesting (normal sequestration site) but not core immune function
- [ ] PMID:25692704 provides evidence
- [ ] Keep but label as developmental/structural context rather than immune function

Rows 26-27: Endocytic vesicle and apical localization
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Likely represent trafficking during activation
- [ ] Keep but mark as supplementary cellular context

Checklist for STA-2

DBL-1 (G5EEL5) - 32 annotations (Priority: MEDIUM)

Critical Issue

ISSUE 1: Rows 15-16 Duplicate
- [ ] Row 15: GO:0050829 (defense response to Gram-negative bacterium) IMP PMID:17975555
- [ ] Row 16: GO:0050829 (same) IMP PMID:17975555 (exact duplicate)
- [ ] Action: CONSOLIDATE - Remove row 16, keep row 15
- [ ] Verify that consolidation doesn't lose any unique information (same ref, evidence, GO term)

Growth/Development Annotations - Categorize as NON-CORE

Rows 21, 26-27, 32: GO:0040018 (positive regulation of multicellular organism growth)
- [ ] Status: KEEP_AS_NON_CORE (4 entries)
- [ ] Core to dbl-1 biology but peripheral to surveillance immunity
- [ ] Mark as developmental role, not immune

Row 28: GO:0045138 (nematode male tail tip morphogenesis) - IMP
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Well-documented but not immune-related

Row 30: GO:0045793 (positive regulation of cell size) - IMP
- [ ] Status: KEEP_AS_NON_CORE

Row 31: GO:0046622 (positive regulation of organ growth) - IMP
- [ ] Status: KEEP_AS_NON_CORE

Row 29: GO:0002119 (nematode larval development) - IMP
- [ ] Status: KEEP_AS_NON_CORE

Row 23: GO:0032877 (positive regulation of DNA endoreduplication) - IMP
- [ ] Status: KEEP_AS_NON_CORE

Row 12: GO:0042661 (regulation of mesodermal cell fate specification) - IGI
- [ ] Status: KEEP_AS_NON_CORE

Immune Response Annotations - ACCEPT

Row 14: GO:0050832 (defense response to fungus) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:19198592
- [ ] Core immune function

Rows 15-17: Bacterial Defense (Gram-negative and Gram-positive)
- [ ] Row 15: GO:0050829 Gram-negative - ACCEPT
- [ ] Row 16: DUPLICATE - REMOVE
- [ ] Row 17: GO:0050830 Gram-positive - ACCEPT
- [ ] All IMP with PMID:17975555

Row 22: GO:0045087 (innate immune response) - IMP
- [ ] Status: ACCEPT
- [ ] PMID:19198592
- [ ] Core immune annotation

Core TGF-beta/BMP Pathway - ACCEPT

Row 2: GO:0005125 (cytokine activity) - IBA
- [ ] Status: ACCEPT
- [ ] Phylogenetically appropriate for TGF-beta family

Rows 4, 19: GO:0030509 (BMP signaling pathway) - IBA, ISS
- [ ] Status: ACCEPT (both entries)
- [ ] Core molecular function

Row 6: GO:0008083 (growth factor activity) - IEA
- [ ] Status: ACCEPT

Row 20: GO:0070700 (BMP receptor binding) - ISS
- [ ] Status: ACCEPT
- [ ] Phylogenetically appropriate

Rows 3, 5: Extracellular localization
- [ ] Row 3: GO:0005615 (extracellular space) is_active_in IBA - ACCEPT
- [ ] Row 5: GO:0005576 (extracellular region) IEA - ACCEPT

Miscellaneous Annotations

Row 7: GO:0010628 (positive regulation of gene expression) - IMP
- [ ] Status: ACCEPT (in immune context with PMID:18158917)

Row 8: GO:0019216 (regulation of lipid metabolic process) acts_upstream_of - IMP
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Secondary metabolic role

Row 9: GO:0022604 (regulation of cell morphogenesis) - IMP
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Non-immune context

Row 10: GO:0045944 (positive regulation of transcription by RNA pol II) - IMP
- [ ] Status: MODIFY or CONSOLIDATE
- [ ] Check if this is redundant with immune pathway activation (row 14 or 22)
- [ ] May consolidate if captured by more specific immune term

Row 11: GO:0030511 (positive regulation of TGF-beta receptor signaling) - IGI
- [ ] Status: ACCEPT
- [ ] Pathway component annotation

Row 24-25: Growth regulation - IGI entries
- [ ] Status: KEEP_AS_NON_CORE
- [ ] Genetic interaction evidence but developmental context

Checklist for DBL-1

DAF-16 (O16850) - 144 annotations (Priority: CRITICAL - LARGEST)

Overview

With 144 annotations, this is the most complex review. Focus on:
1. Critical errors (generic protein binding, pseudokinase-like over-annotations)
2. Consolidation of redundant entries (lifespan appears 13+ times)
3. Categorization of core vs. non-core functions
4. Standardization of relationships (localization)

CRITICAL ISSUE 1: Generic "Protein Binding" Annotations (8-9 entries)

Rows 25-32: GO:0005515 (protein binding) - IPI
- [ ] Total: 8 entries with IPI evidence
- [ ] Action: REVIEW AND REPLACE with specific binding interactions OR REMOVE

Row With/From Gene PMID Action Replace with
25 Q17941 15068796 MAP or REMOVE Specific binding term or remove
26 Q2PJ68 15068796 MAP or REMOVE Specific binding term or remove
27 Q9XTG7 15068796 MAP or REMOVE Specific binding term or remove
28 Q21921 16777605 REVIEW If FKH-1: keep as forkhead-forkhead interaction
29 Q21921 16860373 REVIEW If FKH-1: keep as forkhead-forkhead interaction
30 Q17941 18358814 MAP or REMOVE Specific binding term or remove
31 Q2PJ68 18358814 MAP or REMOVE Specific binding term or remove
32 Q9XTG7 18358814 MAP or REMOVE Specific binding term or remove

Additional protein binding entries:
- [ ] Row 108: GO:0005515 IPI PMID:23255046 UniProtKB:Q17075 - REVIEW
- [ ] Row 140: GO:0005515 IPI PMID:11124266 UniProtKB:P63101 - KEEP (if 14-3-3)

Action Plan:
1. [ ] Check UniProt interaction database or cited publications for each with/from gene
2. [ ] For rows 25-27, 30-32: Likely high-throughput data; either REMOVE or annotate specifically
3. [ ] For rows 28-29: IF Q21921 is FKH-1, convert to GO:0140297 (DNA-binding transcription factor binding)
4. [ ] For row 140: IF P63101 is 14-3-3, already specific as GO:0071889 exists (rows 56, 76)
5. [ ] For rows 56, 76: GO:0071889 (14-3-3 protein binding) - KEEP both (PMID:17098225, PMID:21531333)

CRITICAL ISSUE 2: Lifespan Annotation Consolidation (13+ entries)

GO:0008340 (determination of adult lifespan) appears at rows: 15, 50, 70, 84-86, 89, 95, 100, 111-112, 114, 133-134, 142-143

Row Evidence PMID Action
15 IEA - REMOVE (weak, ARBA:ARBA00026742)
50 IMP 11747825 KEEP
70 IMP 23665919 KEEP
84 IMP 17277769 REVIEW - older but solid
85 IGI 17277769 KEEP (with gentic modifier)
86 IGI 27001890 KEEP (with WB:WBGene00001609)
89 IMP 27564576 KEEP
95 IMP 23352664 KEEP
100 IMP 15905404 KEEP
111 IDA 22922647 KEEP (direct assay)
112 IMP 22560223 REVIEW - may consolidate with others
114 IGI 20523893 KEEP
133 IMP 11381260 REVIEW - older but foundational
134 IMP 11747821 REVIEW - older but foundational
142 IMP 11381260 DUPLICATE of 133 (same PMID)
143 IGI 11381260 DUPLICATE source (same PMID as 142)

Action Plan:
1. [ ] Remove row 15 (weak IEA evidence)
2. [ ] Remove row 142 (exact duplicate of row 133)
3. [ ] Consolidate rows 143 and other IGI entries with same PMID into single entry
4. [ ] Keep strongest evidence: rows 50, 70, 89, 95, 100, 111 (IMP/IDA)
5. [ ] Consolidate genetic interactions (IGI) to representative examples
6. [ ] Target: Reduce 13+ entries to 6-8 core entries maintaining evidence diversity

ISSUE 3: Developmental Annotations - Categorize as NON-CORE (20 entries)

Dauer-related (GO:0040024, GO:0061065, GO:0061066, GO:1905909):
- [ ] Rows 68-69, 83, 92-93, 102, 105: All KEEP_AS_NON_CORE
- [ ] Mark as developmental role
- [ ] These are well-documented but not core to surveillance immunity

Larval development (GO:0002119):
- [ ] Row 125: KEEP_AS_NON_CORE
- [ ] PMID:11747821 (IMP)

Synaptic assembly (GO:0008582, GO:0045887):
- [ ] Rows 71-73: KEEP_AS_NON_CORE
- [ ] PMID:23665919 (IGI)
- [ ] Neuromuscular junction development

Sleep (GO:0030431):
- [ ] Rows 59-60: KEEP_AS_NON_CORE
- [ ] PMID:29523076 (IGI)

Memory (GO:0007614):
- [ ] Row 94: KEEP_AS_NON_CORE
- [ ] PMID:26675724 (IGI)

Muscle development (GO:0060537):
- [ ] Row 124: KEEP_AS_NON_CORE
- [ ] PMID:18397876 (IMP)

ISSUE 4: Localization Annotations - Standardize (8-10 entries for nucleus/cytoplasm)

Nuclear localization (GO:0005634):
- [ ] Rows 3 (is_active_in, IBA)
- [ ] Rows 33, 43-47, 55, 77, 87, 109, 119, 127-128: Multiple IDA entries
- [ ] Row 10 (located_in, IEA)

Action:
1. [ ] Keep row 3 (is_active_in for transcriptional function)
2. [ ] Consolidate IDA entries to 2-3 strongest (PMID:11124266, PMID:11381260, PMID:11747821)
3. [ ] Remove redundant NAS entries (rows 33) if IDA exists
4. [ ] Remove IEA entries (row 10) if IBA/IDA exist

Cytoplasmic localization (GO:0005737):
- [ ] Rows 11 (IEA located_in)
- [ ] Rows 34-35 (NAS located_in)
- [ ] Row 78 (IDA located_in)
- [ ] Row 88 (colocalizes_with IDA)
- [ ] Row 129-130 (IDA located_in)

Action:
1. [ ] Keep IDA entries (rows 78, 129-130): empirical evidence
2. [ ] Consolidate NAS entries (rows 34-35) or remove if IDA available
3. [ ] Remove IEA entry (row 11)
4. [ ] Standardize: Use is_active_in for nucleus (transcription), located_in for both (subcellular)

ISSUE 5: Broad Process Terms - Convert to Specific

GO:0010468 (regulation of gene expression):
- [ ] Row 58: MODIFY to more specific term
- [ ] PMID:32963007 (IMP)
- [ ] Replace with specific process (e.g., GO:0045087 innate immune, GO:0008286 insulin pathway, etc.)

GO:0006355 (regulation of DNA-templated transcription):
- [ ] Rows 13, 120, 131 (IEA or IDA)
- [ ] These are parent terms of more specific annotations
- [ ] KEEP row 13 (IBA broad parent term OK), REMOVE rows 120-131 (redundant with IDA annotations below)

GO:0006351 (DNA-templated transcription):
- [ ] Row 12 (IEA)
- [ ] Extremely generic; REMOVE or keep as parent term only

ISSUE 6: Core Immune Annotations - ACCEPT (Priority to RETAIN)

Innate immune response:
- [ ] Row 23: GO:0045087 IEA - ACCEPT
- [ ] Row 115: GO:0045087 IMP PMID:19454349 - ACCEPT PRIMARY

Defense response annotations:
- [ ] Row 57: GO:0050829 (Gram-negative) IGI - ACCEPT
- [ ] Row 63: GO:0050829 IMP - ACCEPT
- [ ] Row 117: GO:0050829 IMP - ACCEPT
- [ ] Row 67: GO:0050830 (Gram-positive) IMP - ACCEPT
- [ ] Row 98: GO:1900426 (positive regulation of defense response to bacterium) IMP - ACCEPT

Oxidative stress response:
- [ ] Row 19: GO:0009896 (positive regulation of catabolic) - ACCEPT (stress metabolism)
- [ ] Row 39: GO:0034605 (cellular response to heat) NAS - ACCEPT
- [ ] Row 79: GO:0006979 (response to oxidative stress) IGI - ACCEPT
- [ ] Row 101: GO:0034599 (cellular response to oxidative stress) IGI - ACCEPT
- [ ] Row 138-139: GO:0034605 (cellular response to heat) IDA - ACCEPT

Starvation response:
- [ ] Row 21: GO:0042594 (response to starvation) IEA - ACCEPT
- [ ] Row 97: GO:0042594 IMP - ACCEPT

UV response:
- [ ] Row 80: GO:0009411 (response to UV) IGI - ACCEPT
- [ ] Row 135: GO:0009411 IDA - ACCEPT

Apoptosis:
- [ ] Row 122: GO:0043065 (positive regulation of apoptosis) IMP - ACCEPT (stress response)

Positive regulation of immune response:
- [ ] Row 18: GO:0031349 (positive regulation of defense response) IEA - ACCEPT
- [ ] Row 24: GO:0050778 (positive regulation of immune response) IEA - ACCEPT
- [ ] Row 116: GO:0045944 (positive regulation of transcription) IMP - ACCEPT

ISSUE 7: DNA Binding Annotations - Consolidate (6-8 entries)

Row GO Term Evidence Action
2 GO:0000981 (Pol II TF activity) IBA KEEP PRIMARY
5 GO:0000978 (Pol II cis-reg binding) IBA KEEP
8 GO:0003677 (DNA binding) IEA REMOVE (parent)
9 GO:0003700 (TF activity) IEA KEEP as secondary
22 GO:0043565 (sequence-specific DNA binding) IEA KEEP (specific)
41-42 GO:0000978 IDA KEEP (2 entries with different studies)
48 GO:0001228 (activator activity Pol II) IDA KEEP
53 GO:0000978 IDA CONSOLIDATE with 41-42
54 GO:0000981 IMP KEEP
62 GO:0000977 (TRR sequence-specific binding) IDA KEEP
106 GO:0003700 IDA REMOVE (duplicate of 9)

Action Plan:
1. [ ] Keep rows 2, 5 (IBA core TF activities)
2. [ ] Remove row 8 (GO:0003677 too generic)
3. [ ] Keep row 22 (sequence-specific binding specific)
4. [ ] Consolidate IDA entries (41-42, 53, 62) into representative example(s)
5. [ ] Target: Reduce to 5-6 core DNA binding annotations

Checklist for DAF-16 (PARTIAL - focusing on critical issues)

Final Implementation Steps (All Genes)

Step 1: Systematic Review (Week 1-2)

Step 2: Update Review YAML Files

For each gene, update the existing_annotations section:
- [ ] Add/modify review subsections with updated actions
- [ ] Update summary field to justify action
- [ ] Complete reason field with rationale
- [ ] Update supported_by with exact supporting text quotes

Step 3: Add New Annotations (Only for clec-60 + identified gaps)

Step 4: Core Functions Update

Step 5: Validation and Commit

Step 6: Final Review Pass

Success Metrics

Completion targets:
- [ ] All 6 genes reviewed with detailed rationale for each action
- [ ] Critical errors fixed (protein binding, pseudokinase annotations, lysozyme activity)
- [ ] At least 30-40% reduction in low-quality annotations (generic terms, weak evidence)
- [ ] Core immune functions clearly identified and retained
- [ ] All changes documented and committed

Quality indicators:
- [ ] >80% of remaining annotations have IMP/IGI/IDA evidence or strong IBA support
- [ ] <5% of remaining annotations are generic terms (protein binding, regulation of transcription)
- [ ] Core immune functions well-represented across all 6 genes
- [ ] Non-core developmental roles clearly marked and organized

Last Updated: 2025-12-29
Next Review Due: After all YAML updates complete and validated