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Variant Analysis and Annotation · FreedomIntelligence | DecimalAI

Scienceby FreedomIntelligence

Variant Analysis and Annotation

Production-ready VCF processing, variant annotation, mutation analysis, and structural variant (SV/CNV) interpretation for bioinformatics questions. Parses VCF files (streaming, large files), classifies mutation types (missense, nonsense, synonymous, frameshift, splice, intronic, intergenic) and structural variants (deletions, duplications, inversions, translocations), applies VAF/depth/quality/consequence filters, annotates with ClinVar/dbSNP/gnomAD/CADD via ToolUniverse, interprets SV/CNV clin

SkillScore

SkillScore50/100

Test results 50

Safety

3/3 safety checks passed

Code scan
Intent
Content

What it changes

17%50%of test cases passed +33 pts

Without skill4 of 24

With skill12 of 24

8 fixed4 passed either way12 still failing0 broke

Measured on gemini-3.6-flash7/26/2026v121 comparable

Track record

Agent runs: 0; All time

Use this skill

Your agent runs on

Adds every file the skill has, pinned so you can update it. No account needed.

pip install "decimalai>=0.15"
decimalai skills add tooluniverse-variant-analysis
claude --plugin-dir "$(git rev-parse --show-toplevel 2>/dev/null || pwd)/.agents"

The same install from Python, for a notebook or a setup script.

Install

pip install "decimalai>=0.15"

Add the skill

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

print("Added. Start Claude Code with the command below.")

Start Claude Code with it

claude --plugin-dir "$(git rev-parse --show-toplevel 2>/dev/null || pwd)/.agents"

Type these in a Claude Code session. No account or API key. It writes the skill and any files it bundles, and asks first when its safety rating isn't Passed.

Add the DecimalAI plugin, once

/plugin marketplace add decimal-labs/decimalai-claude-plugins
/plugin install decimalai@decimalai

Install this skill

/decimalai:install tooluniverse-variant-analysis

The plugin needs python3 and curl on your machine.

No Python or account. Claude Code picks it up in its next session.

Save it into your project

curl -fsSL --create-dirs -o .claude/skills/tooluniverse-variant-analysis/SKILL.md https://app.decimal.ai/s/tooluniverse-variant-analysis/SKILL.md

Copy SKILL.md

Save it in your project, as

.claude/skills/tooluniverse-variant-analysis/SKILL.md

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Claude Code docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[claude-agent-sdk]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import asyncio

from claude_agent_sdk import ClaudeAgentOptions
from decimalai.claude_agent_sdk import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

async def main():
    question = "Hello!"
    async with support.run(question) as run:  # one user message, one run
        async for message in run.query(options=ClaudeAgentOptions(max_turns=6)):
            print(message)

# In a notebook or async code: await main()
asyncio.run(main())

Prefer its own loader? ClaudeAgentOptions(plugins=[skills_plugin()], skills="all") reads the same folder. Use one or the other: a skill delivered both ways reaches the prompt twice.

The same install from Python, for a notebook or a setup script. agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[claude-agent-sdk]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import asyncio

from claude_agent_sdk import ClaudeAgentOptions
from decimalai.claude_agent_sdk import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

async def main():
    question = "Hello!"
    async with support.run(question) as run:  # one user message, one run
        async for message in run.query(options=ClaudeAgentOptions(max_turns=6)):
            print(message)

# In a notebook or async code: await main()
asyncio.run(main())

Prefer its own loader? ClaudeAgentOptions(plugins=[skills_plugin()], skills="all") reads the same folder. Use one or the other: a skill delivered both ways reaches the prompt twice.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

import asyncio
from pathlib import Path
from claude_agent_sdk import ClaudeAgentOptions, query

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
options = ClaudeAgentOptions(system_prompt=f"You are a helpful agent.\n\n{skill}", max_turns=6)

async def main():
    async for message in query(prompt="Hello!", options=options):
        print(message)

# In a notebook or async code: await main()
asyncio.run(main())

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Claude Agent SDK docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[openai-agents]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from agents import Agent, Runner
from decimalai.openai_agents import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = Agent(
    name=support.name,
    instructions=support.instructions,  # your prompt, then the skill list
    tools=[*support.tools],             # your tools, then load_skill
)
# In a notebook or async code: result = await Runner.run(agent, "Hello!")
result = Runner.run_sync(agent, "Hello!")

Using SandboxAgent? capabilities=[Shell(), decimalai.openai_agents.sandbox_skills()] points its own loader at the same folder.

Install

pip install "decimalai[openai-agents]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from agents import Agent, Runner
from decimalai.openai_agents import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = Agent(
    name=support.name,
    instructions=support.instructions,  # your prompt, then the skill list
    tools=[*support.tools],             # your tools, then load_skill
)
# In a notebook or async code: result = await Runner.run(agent, "Hello!")
result = Runner.run_sync(agent, "Hello!")

Using SandboxAgent? capabilities=[Shell(), decimalai.openai_agents.sandbox_skills()] points its own loader at the same folder.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from agents import Agent, Runner

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = Agent(name="support", instructions=f"You are a helpful agent.\n\n{skill}")
# In a notebook or async code: result = await Runner.run(agent, "Hello!")
result = Runner.run_sync(agent, "Hello!")

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

OpenAI Agents docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[openai]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import json

from openai import OpenAI
from decimalai.openai import agent_config

client = OpenAI()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")


def lookup_order(order_id: str) -> str:
    return f"Order {order_id} shipped yesterday."


# Your tools, as Chat Completions takes them, and what answers each.
TOOLS = [{"type": "function", "function": {
    "name": "lookup_order",
    "description": "Look up the status of an order.",
    "parameters": {"type": "object", "properties": {"order_id": {"type": "string"}},
                   "required": ["order_id"]},
}}]
FUNCTIONS = {"lookup_order": lookup_order}

question = "Where is order A1001?"
with support.run(question) as run:  # one user message, one run
    # run.system is your prompt, then the skill list.
    messages = [{"role": "system", "content": run.system}, run.message]
    while True:
        reply = client.chat.completions.create(
            model="gpt-5.4-mini",
            messages=messages,
            tools=[*TOOLS, *run.tools],  # your tools, then load_skill
        ).choices[0].message
        messages.append(reply)
        if not reply.tool_calls:
            break
        for call in reply.tool_calls:
            # load_skill is answered by the run; your own tools by FUNCTIONS.
            function = FUNCTIONS.get(call.function.name)
            messages.append(run.tool_result(call) or {
                "role": "tool", "tool_call_id": call.id,
                "content": function(**json.loads(call.function.arguments)) if function
                else f"There is no tool named {call.function.name!r}.",
            })
print(reply.content)

# The Responses API takes run.response_tools instead of run.tools.

Install

pip install "decimalai[openai]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import json

from openai import OpenAI
from decimalai.openai import agent_config

client = OpenAI()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")


def lookup_order(order_id: str) -> str:
    return f"Order {order_id} shipped yesterday."


# Your tools, as Chat Completions takes them, and what answers each.
TOOLS = [{"type": "function", "function": {
    "name": "lookup_order",
    "description": "Look up the status of an order.",
    "parameters": {"type": "object", "properties": {"order_id": {"type": "string"}},
                   "required": ["order_id"]},
}}]
FUNCTIONS = {"lookup_order": lookup_order}

question = "Where is order A1001?"
with support.run(question) as run:  # one user message, one run
    # run.system is your prompt, then the skill list.
    messages = [{"role": "system", "content": run.system}, run.message]
    while True:
        reply = client.chat.completions.create(
            model="gpt-5.4-mini",
            messages=messages,
            tools=[*TOOLS, *run.tools],  # your tools, then load_skill
        ).choices[0].message
        messages.append(reply)
        if not reply.tool_calls:
            break
        for call in reply.tool_calls:
            # load_skill is answered by the run; your own tools by FUNCTIONS.
            function = FUNCTIONS.get(call.function.name)
            messages.append(run.tool_result(call) or {
                "role": "tool", "tool_call_id": call.id,
                "content": function(**json.loads(call.function.arguments)) if function
                else f"There is no tool named {call.function.name!r}.",
            })
print(reply.content)

# The Responses API takes run.response_tools instead of run.tools.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from openai import OpenAI

client = OpenAI()
skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
reply = client.chat.completions.create(
    model="gpt-5.4-mini",
    messages=[
        {"role": "system", "content": f"You are a helpful agent.\n\n{skill}"},
        {"role": "user", "content": "Hello!"},
    ],
).choices[0].message

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

OpenAI SDK docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[anthropic]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import anthropic
from decimalai.anthropic import agent_config

client = anthropic.Anthropic()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

question = "Hello!"
with support.run(question) as run:  # one user message, one run
    answer = client.beta.messages.tool_runner(
        model="claude-haiku-5-5",
        max_tokens=4096,
        system=run.system,     # your prompt, then the skill list
        tools=[*run.tools],    # your tools, then load_skill
        messages=[{"role": "user", "content": question}],
    ).until_done()

Install

pip install "decimalai[anthropic]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import anthropic
from decimalai.anthropic import agent_config

client = anthropic.Anthropic()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

question = "Hello!"
with support.run(question) as run:  # one user message, one run
    answer = client.beta.messages.tool_runner(
        model="claude-haiku-5-5",
        max_tokens=4096,
        system=run.system,     # your prompt, then the skill list
        tools=[*run.tools],    # your tools, then load_skill
        messages=[{"role": "user", "content": question}],
    ).until_done()

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
import anthropic

client = anthropic.Anthropic()
skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
reply = client.messages.create(
    model="claude-haiku-5-5",
    max_tokens=4096,
    system=f"You are a helpful agent.\n\n{skill}",
    messages=[{"role": "user", "content": "Hello!"}],
)

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Anthropic docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[google-genai]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from google import genai
from google.genai import types
from decimalai.google_genai import agent_config

client = genai.Client()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")


def lookup_order(order_id: str) -> str:
    return f"Order {order_id} shipped yesterday."


# Your functions, as declarations for the model, and what answers each.
TOOLS = [{"function_declarations": [{
    "name": "lookup_order",
    "description": "Look up the status of an order.",
    "parameters_json_schema": {"type": "object", "properties": {"order_id": {"type": "string"}},
                               "required": ["order_id"]},
}]}]
FUNCTIONS = {"lookup_order": lookup_order}

question = "Where is order A1001?"
with support.run(question) as run:  # one user message, one run
    config = types.GenerateContentConfig(
        system_instruction=run.system,     # your prompt, then the skill list
        tools=[*TOOLS, *run.tool_params],  # your functions, then load_skill
    )
    contents = [{"role": "user", "parts": [{"text": run.message}]}]
    while True:
        response = client.models.generate_content(
            model="gemini-3.5-flash", contents=contents, config=config,
        )
        if not response.function_calls:
            break
        contents.append(response.candidates[0].content)
        parts = []
        for call in response.function_calls:
            # load_skill is answered by the run; your own functions by FUNCTIONS.
            # A loop of your own rather than automatic function calling, which
            # raises KeyError when the model asks for a function you did not pass.
            function = FUNCTIONS.get(call.name)
            parts.append(run.tool_result(call) or {"function_response": {
                "name": call.name, "id": call.id,
                "response": {"result": function(**(call.args or {})) if function
                             else f"There is no function named {call.name!r}."},
            }})
        contents.append({"role": "user", "parts": parts})
print(response.text)

Install

pip install "decimalai[google-genai]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from google import genai
from google.genai import types
from decimalai.google_genai import agent_config

client = genai.Client()
# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")


def lookup_order(order_id: str) -> str:
    return f"Order {order_id} shipped yesterday."


# Your functions, as declarations for the model, and what answers each.
TOOLS = [{"function_declarations": [{
    "name": "lookup_order",
    "description": "Look up the status of an order.",
    "parameters_json_schema": {"type": "object", "properties": {"order_id": {"type": "string"}},
                               "required": ["order_id"]},
}]}]
FUNCTIONS = {"lookup_order": lookup_order}

question = "Where is order A1001?"
with support.run(question) as run:  # one user message, one run
    config = types.GenerateContentConfig(
        system_instruction=run.system,     # your prompt, then the skill list
        tools=[*TOOLS, *run.tool_params],  # your functions, then load_skill
    )
    contents = [{"role": "user", "parts": [{"text": run.message}]}]
    while True:
        response = client.models.generate_content(
            model="gemini-3.5-flash", contents=contents, config=config,
        )
        if not response.function_calls:
            break
        contents.append(response.candidates[0].content)
        parts = []
        for call in response.function_calls:
            # load_skill is answered by the run; your own functions by FUNCTIONS.
            # A loop of your own rather than automatic function calling, which
            # raises KeyError when the model asks for a function you did not pass.
            function = FUNCTIONS.get(call.name)
            parts.append(run.tool_result(call) or {"function_response": {
                "name": call.name, "id": call.id,
                "response": {"result": function(**(call.args or {})) if function
                             else f"There is no function named {call.name!r}."},
            }})
        contents.append({"role": "user", "parts": parts})
print(response.text)

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from google import genai
from google.genai import types

client = genai.Client()
skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
response = client.models.generate_content(
    model="gemini-3.5-flash",
    contents="Hello!",
    config=types.GenerateContentConfig(system_instruction=f"You are a helpful agent.\n\n{skill}"),
)

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Gemini API docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[langchain]" langchain-openai
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from langchain.agents import create_agent
from decimalai.langchain import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = create_agent(
    "openai:gpt-5.4-mini",
    tools=[],                         # your tools; the middleware adds load_skill
    middleware=[support.middleware],  # your prompt, the skill list and load_skill
)
result = agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

Install

pip install "decimalai[langchain]" langchain-openai

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from langchain.agents import create_agent
from decimalai.langchain import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = create_agent(
    "openai:gpt-5.4-mini",
    tools=[],                         # your tools; the middleware adds load_skill
    middleware=[support.middleware],  # your prompt, the skill list and load_skill
)
result = agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from langchain.agents import create_agent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = create_agent("openai:gpt-5.4-mini", tools=[], system_prompt=f"You are a helpful agent.\n\n{skill}")
result = agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

LangChain docs

CrewAI's own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" "crewai>=1.15.27"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import decimalai.crewai
from crewai import Agent, Crew, Task

agent = Agent(
    role="Support", goal="Help the customer", backstory="A support agent.",
    llm=llm,                               # your own CrewAI LLM
    skills=decimalai.crewai.skills(),      # the installed folder
    tools=decimalai.crewai.skill_tools(),  # reads a skill's files, runs its scripts
)
task = Task(description="Hello!", expected_output="an answer", agent=agent)
Crew(agents=[agent], tasks=[task]).kickoff()

The same install from Python, for a notebook or a setup script. CrewAI's own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" "crewai>=1.15.27"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import decimalai.crewai
from crewai import Agent, Crew, Task

agent = Agent(
    role="Support", goal="Help the customer", backstory="A support agent.",
    llm=llm,                               # your own CrewAI LLM
    skills=decimalai.crewai.skills(),      # the installed folder
    tools=decimalai.crewai.skill_tools(),  # reads a skill's files, runs its scripts
)
task = Task(description="Hello!", expected_output="an answer", agent=agent)
Crew(agents=[agent], tasks=[task]).kickoff()

No DecimalAI package. CrewAI's own loader reads the folder, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from crewai import Agent, Crew, Task

agent = Agent(
    role="Support", goal="Help the customer", backstory="A support agent.",
    llm=llm,                         # your own CrewAI LLM
    skills=[Path(".agents/skills")],
)
task = Task(description="Hello!", expected_output="an answer", agent=agent)
Crew(agents=[agent], tasks=[task]).kickoff()

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

CrewAI docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[adk]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from decimalai.adk import DecimalAIPlugin, agent_config
from google.adk.agents import LlmAgent
from google.adk.apps import App

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = LlmAgent(
    name="support",          # ADK needs a Python identifier
    model="gemini-3.5-flash",
    instruction=support.instruction,  # your prompt, then the skill list
    tools=[*support.tools],           # your tools, then load_skill
)
# DecimalAIPlugin makes each invocation of runners built from this App one trace.
app = App(name="support", root_agent=agent, plugins=[DecimalAIPlugin()])

Prefer ADK's own loader? SkillToolset(skills=decimalai.adk.skills(), ...) reads the same folder. Use one or the other: a skill delivered both ways reaches the prompt twice.

Install

pip install "decimalai[adk]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from decimalai.adk import DecimalAIPlugin, agent_config
from google.adk.agents import LlmAgent
from google.adk.apps import App

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = LlmAgent(
    name="support",          # ADK needs a Python identifier
    model="gemini-3.5-flash",
    instruction=support.instruction,  # your prompt, then the skill list
    tools=[*support.tools],           # your tools, then load_skill
)
# DecimalAIPlugin makes each invocation of runners built from this App one trace.
app = App(name="support", root_agent=agent, plugins=[DecimalAIPlugin()])

Prefer ADK's own loader? SkillToolset(skills=decimalai.adk.skills(), ...) reads the same folder. Use one or the other: a skill delivered both ways reaches the prompt twice.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from google.adk.agents import LlmAgent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = LlmAgent(
    name="support",
    model="gemini-3.5-flash",
    instruction=lambda context: f"You are a helpful agent.\n\n{skill}",
)

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Google ADK docs

agent_config() hands your agent the skill. With no DecimalAI key it reads your project's files and sends nothing. Needs SDK 0.27 or newer.

Install

pip install "decimalai[pydantic-ai]"
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from pydantic_ai import Agent
from decimalai.pydantic_ai import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = Agent(
    "openai:gpt-4o-mini",
    name=support.name,
    tools=[],                 # your tools; the capability adds load_skill
    capabilities=[support],   # your prompt, the skill list and load_skill
)
# In a notebook or async code: result = await agent.run("Hello!")
result = agent.run_sync("Hello!")

On the Pydantic AI harness, decimalai.pydantic_ai_harness.skills(project) uses its own loader instead.

Install

pip install "decimalai[pydantic-ai]"

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from pydantic_ai import Agent
from decimalai.pydantic_ai import agent_config

# With no DECIMAL_API_KEY this reads the skills your project lists, from disk.
support = agent_config("support", fallback="You are a helpful agent.")

agent = Agent(
    "openai:gpt-4o-mini",
    name=support.name,
    tools=[],                 # your tools; the capability adds load_skill
    capabilities=[support],   # your prompt, the skill list and load_skill
)
# In a notebook or async code: result = await agent.run("Hello!")
result = agent.run_sync("Hello!")

On the Pydantic AI harness, decimalai.pydantic_ai_harness.skills(project) uses its own loader instead.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from pydantic_ai import Agent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = Agent("openai:gpt-4o-mini", instructions=f"You are a helpful agent.\n\n{skill}")
# In a notebook or async code: result = await agent.run("Hello!")
result = agent.run_sync("Hello!")

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Pydantic AI docs

Deep Agents' own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" deepagents
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import decimalai.deepagents
from deepagents import create_deep_agent

agent = create_deep_agent(model=model, **decimalai.deepagents.skills())
agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

The default backend reads files but has no shell. To run a skill's scripts, pass skills(backend=LocalShellBackend(...)).

The same install from Python, for a notebook or a setup script. Deep Agents' own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" deepagents

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import decimalai.deepagents
from deepagents import create_deep_agent

agent = create_deep_agent(model=model, **decimalai.deepagents.skills())
agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

The default backend reads files but has no shell. To run a skill's scripts, pass skills(backend=LocalShellBackend(...)).

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from deepagents import create_deep_agent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = create_deep_agent(model=model, system_prompt=f"You are a helpful agent.\n\n{skill}")
agent.invoke({"messages": [{"role": "user", "content": "Hello!"}]})

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Deep Agents docs

Its own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" agent-framework
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

import asyncio

from agent_framework import Agent
from decimalai.agent_framework import skills

agent = Agent(client=client, instructions="You are a helpful agent.", context_providers=[skills()])
asyncio.run(agent.run("Hello!"))

It caches skills by default, so restart the process after decimalai skills update.

The same install from Python, for a notebook or a setup script. Its own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" agent-framework

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

import asyncio

from agent_framework import Agent
from decimalai.agent_framework import skills

agent = Agent(client=client, instructions="You are a helpful agent.", context_providers=[skills()])
asyncio.run(agent.run("Hello!"))

It caches skills by default, so restart the process after decimalai skills update.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

import asyncio
from pathlib import Path
from agent_framework import Agent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = Agent(client=client, instructions=f"You are a helpful agent.\n\n{skill}")
asyncio.run(agent.run("Hello!"))

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Microsoft Agent Framework docs

Strands' own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" strands-agents
decimalai skills add tooluniverse-variant-analysis

Add it to your agent

from decimalai.strands import skills
from strands import Agent
from strands.vended_tools import file_editor, shell

agent = Agent(
    model=model,                # always pass one: the default is Amazon Bedrock
    system_prompt="You are a helpful agent.",
    tools=[file_editor, shell],
    plugins=[skills()],
)
agent("Hello!")

Strands loads an agent's skills once, so build the agent again after decimalai skills update.

The same install from Python, for a notebook or a setup script. Strands' own skill loader reads the installed folder. No DecimalAI account needed.

Install

pip install "decimalai>=0.16" strands-agents

Add it to your agent

from decimalai import skillpkg

# Writes .agents/skills and .decimal/skills.toml. Safe to run twice.
result = skillpkg.add("tooluniverse-variant-analysis")
if result.exit_code:
    raise SystemExit(result.problems)

from decimalai.strands import skills
from strands import Agent
from strands.vended_tools import file_editor, shell

agent = Agent(
    model=model,                # always pass one: the default is Amazon Bedrock
    system_prompt="You are a helpful agent.",
    tools=[file_editor, shell],
    plugins=[skills()],
)
agent("Hello!")

Strands loads an agent's skills once, so build the agent again after decimalai skills update.

No DecimalAI package. The whole skill goes in every prompt, and nothing pins or updates it.

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

Give it to your agent

from pathlib import Path
from strands import Agent

skill = Path(".agents/skills/tooluniverse-variant-analysis/SKILL.md").read_text()
agent = Agent(model=model, system_prompt=f"You are a helpful agent.\n\n{skill}")
agent("Hello!")

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Strands docs

Adds every file the skill has, pinned so you can update it. Cursor, Copilot, Cline and Warp read this folder by themselves.

pip install "decimalai>=0.15"
decimalai skills add tooluniverse-variant-analysis

No Python or account. Cursor, Copilot, Cline and Warp read this folder by themselves.

Save it into your project

curl -fsSL --create-dirs -o .agents/skills/tooluniverse-variant-analysis/SKILL.md https://app.decimal.ai/s/tooluniverse-variant-analysis/SKILL.md

Copy SKILL.md

Save it in your project, as

.agents/skills/tooluniverse-variant-analysis/SKILL.md

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Cursor and other editors docs

Fetch the file and give its text to your model as instructions. No account or package needed.

Get the file

curl -fsSL https://app.decimal.ai/s/tooluniverse-variant-analysis/SKILL.md

Read the summary as JSON

curl -fsSL https://app.decimal.ai/s/tooluniverse-variant-analysis.json

This gets SKILL.md only. The skill's 7 other files are not included.

Other ways to add it

Other setups docs

You don't need a DecimalAI account.

Version: v1, tested 7/26/2026
Source: FreedomIntelligence/OpenClaw-Medical-Skills ↗
License: Not recorded

Manage it in DecimalAI

Saved prompts and skills, pinned versions, and traces of this skill in your runs. DecimalAI does not run your agent.

Claude Code reads files from your project, so DecimalAI config does not apply there.

On Claude Agent SDK: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On OpenAI Agents: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On OpenAI SDK: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On Anthropic: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On Gemini API: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On LangChain: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On CrewAI: set DECIMAL_API_KEY and add decimalai.init(crewai=True) to record runs and skill use. The skill version stays in your repo.

On Google ADK: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On Pydantic AI: save the skill to an agent here, set DECIMAL_API_KEY, and the same code uses it with no command to run. Changes you save reach the next run with no redeploy.

On Deep Agents: set DECIMAL_API_KEY and add decimalai.init(langchain=True) to record runs and skill use. The skill version stays in your repo.

On Microsoft Agent Framework: set DECIMAL_API_KEY and add decimalai.init(otel=True, agent_name="support") to record runs and skill use. The skill version stays in your repo.

On Strands: set DECIMAL_API_KEY and add decimalai.init(otel=True, agent_name="support") to record runs and skill use. The skill version stays in your repo.

Editors read files from your project, so DecimalAI config does not apply there.

Anywhere else: record a use with decimalai.log_skill_activation() inside a trace.

Use this skill

SKILL.md

Variant Analysis and Annotation

Production-ready VCF processing and variant annotation skill combining local bioinformatics computation with ToolUniverse database integration. Designed to answer bioinformatics analysis questions about VCF data, mutation classification, variant filtering, and clinical annotation.

When to Use This Skill

Triggers:

User provides a VCF file (SNV/indel or SV) and asks questions about its contents
Questions about variant allele frequency (VAF) filtering
Mutation type classification queries (missense, nonsense, synonymous, etc.)
Structural variant interpretation requests (deletions, duplications, CNVs)
Variant annotation requests (ClinVar, gnomAD, CADD, dbSNP)
CNV pathogenicity assessment using ClinGen dosage sensitivity
Cohort comparison questions
Population frequency filtering (SNVs or SVs)
Intronic/intergenic variant filtering
Gene dosage sensitivity queries

Example Questions:

"What fraction of variants with VAF < 0.3 are annotated as missense mutations?"
"After filtering intronic/intergenic variants, how many non-reference variants remain?"
"What is the clinical significance of this deletion affecting BRCA1?"
"Which dosage-sensitive genes overlap this 500kb duplication on chr17?"
"How many variants have clinical significance annotations?"
"Compare variant counts between samples"

Core Capabilities

Capability	Description
VCF Parsing	Pure Python + cyvcf2 parsers. VCF 4.x, gzipped, multi-sample, SNV/indel/SV
Mutation Classification	Maps SO terms, SnpEff ANN, VEP CSQ, GATK Funcotator to standard types
VAF Extraction	Handles AF, AD, AO/RO, NR/NV, INFO AF formats
Filtering	VAF, depth, quality, PASS, variant type, mutation type, consequence, chromosome, SV size
Statistics	Ti/Tv ratio, per-sample VAF/depth stats, mutation type distribution, SV size distribution
Annotation	MyVariant.info (aggregates ClinVar, dbSNP, gnomAD, CADD, SIFT, PolyPhen)
SV/CNV Analysis	gnomAD SV population frequencies, DGVa/dbVar known SVs, ClinGen dosage sensitivity
Clinical Interpretation	ACMG/ClinGen CNV pathogenicity classification using haploinsufficiency/triplosensitivity scores
DataFrame	Convert to pandas for advanced analytics
Reporting	Markdown reports with tables and statistics, SV clinical reports

Workflow Overview

Input VCF File (SNVs/indels or SVs)
    |
    v
Phase 1: Parse VCF
    |-- Pure Python parser (any VCF 4.x)
    |-- cyvcf2 parser (faster, C-based)
    |-- Extract: CHROM, POS, REF, ALT, QUAL, FILTER, INFO, FORMAT, samples
    |-- Extract per-sample: GT, VAF, depth
    |-- Extract annotations from INFO (ANN, CSQ, FUNCOTATION)
    |-- Detect variant class: SNV/indel vs SV/CNV
    |
    v
Phase 2: Classify Variants
    |-- Variant type: SNV, INS, DEL, MNV, COMPLEX, SV
    |-- Mutation type: missense, nonsense, synonymous, frameshift, splice, etc.
    |-- Impact: HIGH, MODERATE, LOW, MODIFIER
    |-- SV type: DEL, DUP, INV, BND, CNV (if structural variant)
    |
    v
Phase 3: Apply Filters
    |-- VAF range (min/max)
    |-- Read depth minimum
    |-- Quality threshold
    |-- PASS only
    |-- Variant/mutation type inclusion/exclusion
    |-- Consequence exclusion (intronic, intergenic)
    |-- Population frequency range
    |-- Chromosome selection
    |-- SV size range (for structural variants)
    |
    v
Phase 4: Compute Statistics
    |-- Variant type distribution
    |-- Mutation type distribution
    |-- Impact distribution
    |-- Chromosome distribution
    |-- Ti/Tv ratio (for SNVs)
    |-- Per-sample VAF/depth stats
    |-- Gene mutation counts
    |-- SV size distribution (for structural variants)
    |
    v
Phase 5: Annotate with ToolUniverse (optional)
    |-- MyVariant.info: ClinVar, dbSNP, gnomAD, CADD, SIFT, PolyPhen
    |-- dbSNP: Population frequencies, gene associations
    |-- gnomAD: Population allele frequencies
    |-- Ensembl VEP: Consequence prediction
    |
    v
Phase 6: Generate Report / Answer Question
    |-- Markdown report with tables
    |-- Direct answer to specific question
    |-- DataFrame for downstream analysis
    |
    v
Phase 7: Structural Variant & CNV Analysis (if SV/CNV detected)
    |-- Annotate with gnomAD SV population frequencies
    |-- Query DGVa/dbVar for known SVs (Ensembl)
    |-- Identify affected genes
    |-- Query ClinGen dosage sensitivity (HI/TS scores)
    |-- Classify pathogenicity (Pathogenic/Likely Pathogenic/VUS/Benign)
    |-- Generate SV clinical report with ACMG/ClinGen guidelines

Phase Summaries

Phase 1: VCF Parsing

Use pandas for:

Reading VCF as structured data
Quick exploratory analysis
When you need to manipulate columns and rows

Use python_implementation tools for:

Production parsing with annotation extraction
Multi-sample VCF handling
VAF extraction from FORMAT fields
Large file streaming

Key functions:

vcf_data = parse_vcf("input.vcf")           # Pure Python (always works)
vcf_data = parse_vcf_cyvcf2("input.vcf")    # Fast C-based (if installed)
df = variants_to_dataframe(vcf_data.variants, sample="TUMOR")  # For pandas

Phase 2: Variant Classification

Automatic classification from annotations:

SnpEff ANN field
VEP CSQ field
GATK Funcotator FUNCOTATION field
Standard INFO keys: EFFECT, EFF, TYPE

Mutation types supported: missense, nonsense, synonymous, frameshift, splice_site, splice_region, inframe_insertion, inframe_deletion, intronic, intergenic, UTR_5, UTR_3, upstream, downstream, stop_lost, start_lost

See references/mutation_classification_guide.md for full details

Phase 3: Filtering

Common filtering patterns:

# Somatic-like variants
criteria = FilterCriteria(
    min_vaf=0.05, max_vaf=0.95,
    min_depth=20, pass_only=True,
    exclude_consequences=["intronic", "intergenic", "upstream", "downstream"]
)

# High-confidence germline
criteria = FilterCriteria(
    min_vaf=0.25, min_depth=30, pass_only=True,
    chromosomes=["1", "2", ..., "22", "X", "Y"]
)

# Rare pathogenic candidates
criteria = FilterCriteria(
    min_depth=20, pass_only=True,
    mutation_types=["missense", "nonsense", "frameshift"]
)

See references/vcf_filtering.md for all filter options

Phase 4: Statistics

Use pandas for:

Complex aggregations (groupby, pivot tables)
Custom statistical tests
Data exploration

Use python_implementation for:

Standard variant statistics (Ti/Tv, type distribution)
Per-sample VAF/depth summary
Quick mutation type counts

Phase 5: ToolUniverse Annotation

When to use ToolUniverse annotation tools:

ClinVar clinical significance: Use MyVariant.info or dbSNP tools
Population frequencies: Use MyVariant.info (aggregates gnomAD, ExAC, 1000G)
Pathogenicity scores: Use MyVariant.info (aggregates CADD, SIFT, PolyPhen)
Consequence prediction: Use Ensembl VEP tools

Best practices:

Annotate variants with rsIDs first (most reliable)
Use MyVariant.info for batch annotation (aggregates multiple sources)
Limit to top variants (max_annotate=50-100) to respect rate limits
Query dbSNP/gnomAD directly for specific use cases

Key tools:

MyVariant_query_variants: Batch annotation (ClinVar, dbSNP, gnomAD, CADD)
dbsnp_get_variant_by_rsid: Population frequencies
gnomad_get_variant: Basic variant metadata
EnsemblVEP_annotate_rsid: Consequence prediction

See references/annotation_guide.md for detailed examples

Phase 6: Report Generation

Report includes:

Summary Statistics (total variants, type counts, Ti/Tv)
Mutation Type Distribution (table with counts and percentages)
Impact Distribution
Chromosome Distribution
VAF Distribution (per-sample)
Clinical Significance
Top Mutated Genes
Variant Annotations (ClinVar-annotated variants)

Phase 7: Structural Variant & CNV Analysis

When VCF contains SV calls (SVTYPE=DEL/DUP/INV/BND):

Identify affected genes (from VCF annotation or coordinate overlap)

Query ClinGen dosage sensitivity:

clingen = ClinGen_dosage_by_gene(gene_symbol="BRCA1")
# Returns: haploinsufficiency_score, triplosensitivity_score

Check population frequency:

gnomad_sv = gnomad_get_sv_by_gene(gene_symbol="BRCA1")
# Returns: SVs with AF, AC, AN

Classify pathogenicity:
- Pathogenic: Deletion + HI score = 3, AF < 0.0001
- Likely Pathogenic: Deletion + HI score = 2, AF < 0.001
- VUS: HI/TS score = 0-1, AF 0.001-0.01
- Benign: AF > 0.01

ClinGen dosage score interpretation:

3: Sufficient evidence for dosage pathogenicity (HIGH impact)
2: Some evidence (MODERATE impact)
1: Little evidence (LOW impact)
0: No evidence (MINIMAL impact)
40: Dosage sensitivity unlikely

See references/sv_cnv_analysis.md for full SV workflow

Answering BixBench Questions

Pattern 1: VAF + Mutation Type Fraction

Question: "What fraction of variants with VAF < X are annotated as Y mutations?"

result = answer_vaf_mutation_fraction(
    vcf_path="input.vcf",
    max_vaf=0.3,
    mutation_type="missense",
    sample="TUMOR"
)
# Returns: fraction, total_below_vaf, matching_mutation_type

Pattern 2: Cohort Comparison

Question: "What is the difference in mutation frequency between cohorts?"

result = answer_cohort_comparison(
    vcf_paths=["cohort1.vcf", "cohort2.vcf"],
    mutation_type="missense",
    cohort_names=["Treatment", "Control"]
)
# Returns: cohorts, frequency_difference

Pattern 3: Filter and Count

Question: "After filtering X, how many Y remain?"

result = answer_non_reference_after_filter(
    vcf_path="input.vcf",
    exclude_intronic_intergenic=True
)
# Returns: total_input, non_reference, remaining

ToolUniverse Tools Reference

SNV/Indel Annotation

Tool	When to Use	Parameters	Response
`MyVariant_query_variants`	Batch annotation	`query` (rsID/HGVS)	ClinVar, dbSNP, gnomAD, CADD
`dbsnp_get_variant_by_rsid`	Population frequencies	`rsid`	Frequencies, clinical significance
`gnomad_get_variant`	gnomAD metadata	`variant_id` (CHR-POS-REF-ALT)	Basic variant info
`EnsemblVEP_annotate_rsid`	Consequence prediction	`variant_id` (rsID)	Transcript impact

Structural Variant Annotation

Tool	When to Use	Parameters	Response
`gnomad_get_sv_by_gene`	SV population frequency	`gene_symbol`	SVs with AF, AC, AN
`gnomad_get_sv_by_region`	Regional SV search	`chrom`, `start`, `end`	SVs in region
`ClinGen_dosage_by_gene`	Dosage sensitivity	`gene_symbol`	HI/TS scores, disease
`ClinGen_dosage_region_search`	Dosage-sensitive genes in region	`chromosome`, `start`, `end`	All genes with HI/TS scores
`ensembl_get_structural_variants`	Known SVs from DGVa/dbVar	`chrom`, `start`, `end`, `species`	Clinical significance

See references/annotation_guide.md for detailed tool usage examples

Common Use Patterns

Pattern 1: Quick VCF Summary

Parse VCF, compute statistics, generate report.

report = variant_analysis_pipeline("input.vcf", output_file="report.md")

Pattern 2: Filtered Analysis

Parse VCF, apply multi-criteria filter, compute statistics on filtered set.

report = variant_analysis_pipeline(
    vcf_path="input.vcf",
    filters=FilterCriteria(min_vaf=0.1, min_depth=20, pass_only=True),
    output_file="filtered_report.md"
)

Pattern 3: Annotated Report

Parse VCF, annotate top variants with ClinVar/gnomAD/CADD, generate clinical report.

report = variant_analysis_pipeline(
    vcf_path="input.vcf",
    annotate=True,
    max_annotate=50,
    output_file="annotated_report.md"
)

Pattern 4: BixBench Question Answering

Parse VCF, apply specific filters, compute targeted statistics to answer precise questions.

result = answer_vaf_mutation_fraction(
    vcf_path="input.vcf",
    max_vaf=0.3,
    mutation_type="missense"
)

Pattern 5: Cohort Comparison

Parse multiple VCFs, compare mutation frequencies across cohorts.

result = answer_cohort_comparison(
    vcf_paths=["cohort1.vcf", "cohort2.vcf"],
    mutation_type="missense"
)

When to Use pandas vs python_implementation

Use pandas when:

You need to read VCF as a flat table
You want to do custom aggregations (groupby, pivot)
You need to join with other data
You're doing exploratory data analysis
You want to export to CSV/Excel

Use python_implementation when:

You need production-grade VCF parsing
You need to extract INFO annotations (ANN, CSQ)
You need per-sample VAF/depth extraction
You need to classify mutation types
You need standard variant statistics (Ti/Tv)
You need to integrate with ToolUniverse annotation

Best approach: Use python_implementation for parsing/classification, then convert to DataFrame for custom analysis:

# Parse and classify
vcf_data = parse_vcf("input.vcf")
passing, failing = filter_variants(vcf_data.variants, criteria)

# Convert to DataFrame for custom analysis
df = variants_to_dataframe(passing, sample="TUMOR")

# Now use pandas
missense_high_vaf = df[(df['mutation_type'] == 'missense') & (df['vaf'] >= 0.3)]

Limitations

VCF annotation required for mutation classification: If VCF has no ANN/CSQ/FUNCOTATION in INFO, mutation types will be "unknown" until ToolUniverse annotation is applied
Multi-allelic variants: Parser takes first ALT allele for type classification
ToolUniverse annotation rate: API-based, limited to ~100 variants per batch by default to respect rate limits
gnomAD tool: Returns basic metadata only (not full allele frequencies); use MyVariant.info for gnomAD AF
Large VCFs: Pure Python parser streams line-by-line; cyvcf2 is recommended for files with >100K variants

Reference Documentation

references/vcf_filtering.md: Complete filter options and examples
references/mutation_classification_guide.md: Detailed mutation type classification rules
references/annotation_guide.md: ToolUniverse annotation workflows with examples
references/sv_cnv_analysis.md: Complete SV/CNV interpretation workflow

Utility Scripts

scripts/parse_vcf.py: Standalone VCF parsing script
scripts/filter_variants.py: Command-line variant filtering
scripts/annotate_variants.py: Batch variant annotation

Quick Start

See QUICK_START.md for:

Python SDK examples (pipeline, question functions, individual tools)
MCP conversational examples
Common recipes (somatic analysis, clinical screening, population frequency)
Expected output formats
Troubleshooting guide

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skills/tooluniverse-variant-analysis/SKILL.md

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Imported 8/1/2026Version v1Bundled 7 files · scripts

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Other skills for the same job

Published skills whose descriptions closely match this one, with their headline benchmark lift.

mims-harvard/tooluniverse-variant-analysisVCF and variant analysis — parsing, annotation, classification (synonymous, missense, frameshift, stop_gained), VAF filtering, coding vs non-coding categorization, multi-condition variant comparison. Use for VCF parsing, variant fraction calculations (denominator = coding subset only, NOT all variants), and per-sample mutation profiling.Close match-9 pts pass-rate lift

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What it changes

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Use this skill

Variant Analysis and Annotation

When to Use This Skill

Core Capabilities

Workflow Overview

Phase Summaries

Phase 1: VCF Parsing

Phase 2: Variant Classification

Phase 3: Filtering

Phase 4: Statistics

Phase 5: ToolUniverse Annotation

Phase 6: Report Generation

Phase 7: Structural Variant & CNV Analysis

Answering BixBench Questions

Pattern 1: VAF + Mutation Type Fraction

Pattern 2: Cohort Comparison

Pattern 3: Filter and Count

ToolUniverse Tools Reference

SNV/Indel Annotation

Structural Variant Annotation

Common Use Patterns

Pattern 1: Quick VCF Summary

Pattern 2: Filtered Analysis

Pattern 3: Annotated Report

Pattern 4: BixBench Question Answering

Pattern 5: Cohort Comparison

When to Use pandas vs python_implementation

Limitations

Reference Documentation

Utility Scripts

Quick Start

SkillSafety

Source

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