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tooluniverse-protein-modification-analysis

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English
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Translation

Chinese

Protein Post-Translational Modification Analysis

蛋白质翻译后修饰（PTMs）分析

Comprehensive PTM analysis using iPTMnet (primary), ProtVar (functional context), UniProt (baseline), STRING (interactions), ELM (linear motifs), and MassIVE/ProteomeXchange (experimental data).
利用iPTMnet（主要工具）、ProtVar（功能背景）、UniProt（基线数据）、STRING（相互作用）、ELM（线性基序）以及MassIVE/ProteomeXchange（实验数据）进行全面的PTM分析。

LOOK UP DON'T GUESS

查寻而非猜测

  • PTM sites/enzymes: 
    iPTMnet_get_ptm_sites
  • Functional consequence: 
    ProtVar_get_function
    + 
    iPTMnet_get_ptm_ppi
  • Proteoforms: 
    iPTMnet_get_proteoforms
  • Linear motifs: 
    ELM_get_instances
  • PTM位点/酶：
    iPTMnet_get_ptm_sites
  • 功能影响：
    ProtVar_get_function
    + 
    iPTMnet_get_ptm_ppi
  • 蛋白质变体：
    iPTMnet_get_proteoforms
  • 线性基序：
    ELM_get_instances

COMPUTE, DON'T DESCRIBE

计算而非描述

When analysis requires computation (statistics, data processing, scoring, enrichment), write and run Python code via Bash. Don't describe what you would do — execute it and report actual results. Use ToolUniverse tools to retrieve data, then Python (pandas, scipy, statsmodels, matplotlib) to analyze it.
当分析需要计算（统计、数据处理、评分、富集分析）时，通过Bash编写并运行Python代码。不要描述你要做什么——直接执行并报告实际结果。使用ToolUniverse工具获取数据，然后用Python（pandas、scipy、statsmodels、matplotlib）进行分析。

Domain Reasoning

领域推理

PTMs are context-dependent: same phosphorylation site can activate or inhibit depending on kinase and effectors. Always check: which enzyme, what functional consequence, in what cell context.
PTMs具有上下文依赖性：同一个磷酸化位点可能根据激酶和效应物的不同而激活或抑制蛋白质功能。始终要检查：涉及哪种酶、产生什么功能影响、处于何种细胞环境。

KEY PRINCIPLES

核心原则

  1. Disambiguation first -- resolve to UniProt accession before iPTMnet calls
  2. iPTMnet is SOAP-style -- every call requires 
    operation
    parameter
  3. Evidence-graded -- distinguish experimental (T1) from predicted (T4)
  4. English-first queries
  1. 先消歧——在调用iPTMnet之前先解析到UniProt登录号
  2. iPTMnet采用SOAP风格——每次调用都需要
    operation
    参数
  3. 证据分级——区分实验验证（T1）和预测（T4）的结果
  4. 优先英文查询

Workflow

工作流程

Phase 0: Protein Disambiguation → UniProt accession
Phase 1: PTM Site Inventory → iPTMnet_get_ptm_sites
Phase 2: Proteoform Analysis → iPTMnet_get_proteoforms
Phase 3: PTM-Dependent Interactions → iPTMnet_get_ptm_ppi
Phase 4: Functional Context → ProtVar_get_function at key sites
Phase 4b: Linear Motif Context → ELM_get_instances for SLiM overlap
Phase 4c: Experimental Data → MassIVE/ProteomeXchange
Phase 5: Synthesis & Report
Phase 0: 蛋白质消歧 → UniProt登录号
Phase 1: PTM位点清单 → iPTMnet_get_ptm_sites
Phase 2: 蛋白质变体分析 → iPTMnet_get_proteoforms
Phase 3: PTM依赖的相互作用 → iPTMnet_get_ptm_ppi
Phase 4: 功能背景 → 关键位点的ProtVar_get_function
Phase 4b: 线性基序背景 → SLiM重叠区域的ELM_get_instances
Phase 4c: 实验数据 → MassIVE/ProteomeXchange
Phase 5: 综合分析与报告

Phase 0: Disambiguation

Phase 0：消歧

  • iPTMnet_search(operation="search", search_term="TP53", role="Substrate")
    -- find UniProt IDs
  • If user provides UniProt accession directly, use it
  • Select human entry if multiple hits
  • iPTMnet_search(operation="search", search_term="TP53", role="Substrate")
    ——查找UniProt ID
  • 如果用户直接提供UniProt登录号，直接使用该编号
  • 如果有多个结果，选择人类条目

Phase 1: PTM Sites

Phase 1：PTM位点

iPTMnet_get_ptm_sites(operation="get_ptm_sites", uniprot_id="P04637")
-- returns position, residue, modification type, enzyme, evidence. Group by modification type. Fallback: 
UniProt_get_entry_by_accession
PTM annotations.
iPTMnet_get_ptm_sites(operation="get_ptm_sites", uniprot_id="P04637")
——返回位点位置、残基、修饰类型、酶、证据。按修饰类型分组。备选方案：
UniProt_get_entry_by_accession
的PTM注释。

Phase 2: Proteoforms

Phase 2：蛋白质变体

iPTMnet_get_proteoforms(operation="get_proteoforms", uniprot_id=...)
-- distinct PTM combinations. Focus on those with functional/disease annotations if >20.
iPTMnet_get_proteoforms(operation="get_proteoforms", uniprot_id=...)
——不同的PTM组合。如果结果超过20个，重点关注带有功能/疾病注释的变体。

Phase 3: PTM-Dependent Interactions

Phase 3：PTM依赖的相互作用

iPTMnet_get_ptm_ppi(operation="get_ptm_ppi", uniprot_id=...)
-- interacting protein, PTM site, effect (enables/disrupts). Supplement with 
STRING_get_interaction_partners(identifiers=gene, species=9606, required_score=700)
.
iPTMnet_get_ptm_ppi(operation="get_ptm_ppi", uniprot_id=...)
——相互作用蛋白质、PTM位点、效应（激活/破坏）。补充使用
STRING_get_interaction_partners(identifiers=gene, species=9606, required_score=700)
。

Phase 4: Functional Context

Phase 4：功能背景

ProtVar_get_function(accession=..., position=N, variant_aa=AA)
-- domain, active site, binding site, conservation. Grade: active-site PTM > domain-core > disordered region.
ProtVar_get_function(accession=..., position=N, variant_aa=AA)
——结构域、活性位点、结合位点、保守性。优先级：活性位点PTM > 结构域核心 > 无序区域。

Phase 4b: Linear Motifs (ELM)

Phase 4b：线性基序（ELM）

ELM_get_instances(operation="get_instances", uniprot_id=..., motif_type="MOD")
-- MOD = modification sites, DEG = degradation signals. Cross-reference with Phase 1 PTM positions. 
ELM_list_classes(operation="list_classes")
for motif details.
ELM_get_instances(operation="get_instances", uniprot_id=..., motif_type="MOD")
——MOD=修饰位点，DEG=降解信号。与Phase 1的PTM位置交叉验证。使用
ELM_list_classes(operation="list_classes")
获取基序详情。

Phase 4c: Experimental Data

Phase 4c：实验数据

MassIVE_search_datasets(species="9606")
, 
MassIVE_get_dataset(accession="MSV...")
for public MS datasets.
MassIVE_search_datasets(species="9606")
、
MassIVE_get_dataset(accession="MSV...")
用于获取公开的质谱数据集。

Evidence Grading

证据分级

TierCriteria
T1PTM at validated active/binding site with functional data
T2PTM in structured domain with ProtVar annotation
T3Correlation data only (mass spec detection)
T4Predicted, no experimental validation
层级标准
T1经过验证的活性/结合位点的PTM，带有功能数据
T2结构化结构域中的PTM，带有ProtVar注释
T3仅关联数据（质谱检测）
T4预测结果，无实验验证

Tool Parameter Reference

工具参数参考

ToolKey Params
iPTMnet_search
operation="search"
, 
search_term
, 
role
iPTMnet_get_ptm_sites
operation="get_ptm_sites"
, 
uniprot_id
iPTMnet_get_proteoforms
operation="get_proteoforms"
, 
uniprot_id
iPTMnet_get_ptm_ppi
operation="get_ptm_ppi"
, 
uniprot_id
ELM_get_instances
operation="get_instances"
, 
uniprot_id
, 
motif_type
ELM_list_classes
operation="list_classes"
MassIVE_search_datasets
page_size
, 
species
Critical: All iPTMnet and ELM tools require 
operation
as first parameter (SOAP-style).
工具关键参数
iPTMnet_search
operation="search"
, 
search_term
, 
role
iPTMnet_get_ptm_sites
operation="get_ptm_sites"
, 
uniprot_id
iPTMnet_get_proteoforms
operation="get_proteoforms"
, 
uniprot_id
iPTMnet_get_ptm_ppi
operation="get_ptm_ppi"
, 
uniprot_id
ELM_get_instances
operation="get_instances"
, 
uniprot_id
, 
motif_type
ELM_list_classes
operation="list_classes"
MassIVE_search_datasets
page_size
, 
species
重要提示：所有iPTMnet和ELM工具都需要将
operation
作为第一个参数（SOAP风格）。

Fallbacks

备选方案

SituationFallback
Not in iPTMnetUniProt PTM/processing annotations
No PTM-PPI dataSTRING general PPI
No ProtVar dataUniProt domain annotations
No ELM dataProceed with iPTMnet/UniProt only
场景备选方案
不在iPTMnet中UniProt的PTM/加工注释
无PTM-PPI数据STRING的通用PPI数据
无ProtVar数据UniProt的结构域注释
无ELM数据仅使用iPTMnet/UniProt继续分析

Limitations

局限性

  • iPTMnet biased toward well-studied proteins
  • Proteoform data covers observed combinations only
  • PTM-PPI: only PTM-specific evidence; more PPIs exist in STRING
  • iPTMnet偏向于研究充分的蛋白质
  • 蛋白质变体数据仅涵盖已观测到的组合
  • PTM-PPI：仅包含PTM特异性证据；STRING中存在更多的PPI数据