@pikaa-ai/pikaa 0.3.22 → 0.3.24

package/skills/depmap/SKILL.md

@@ -1,301 +0,0 @@
----
-name: depmap
-description: Query the Cancer Dependency Map (DepMap) for cancer cell line gene dependency scores (CRISPR Chronos), drug sensitivity data, and gene effect profiles. Use for identifying cancer-specific vulnerabilities, synthetic lethal interactions, and validating oncology drug targets.
-license: CC-BY-4.0
-metadata:
-  version: "1.0"
-  skill-author: Kuan-lin Huang
----
-
-# DepMap — Cancer Dependency Map
-
-## Overview
-
-The Cancer Dependency Map (DepMap) project, run by the Broad Institute, systematically characterizes genetic dependencies across hundreds of cancer cell lines using genome-wide CRISPR knockout screens (DepMap CRISPR), RNA interference (RNAi), and compound sensitivity assays (PRISM). DepMap data is essential for:
-- Identifying which genes are essential for specific cancer types
-- Finding cancer-selective dependencies (therapeutic targets)
-- Validating oncology drug targets
-- Discovering synthetic lethal interactions
-
-**Key resources:**
-- DepMap Portal: https://depmap.org/portal/
-- DepMap data downloads: https://depmap.org/portal/download/all/
-- Python package: `depmap` (or access via API/downloads)
-- API: https://depmap.org/portal/api/
-
-## When to Use This Skill
-
-Use DepMap when:
-
-- **Target validation**: Is a gene essential for survival in cancer cell lines with a specific mutation (e.g., KRAS-mutant)?
-- **Biomarker discovery**: What genomic features predict sensitivity to knockout of a gene?
-- **Synthetic lethality**: Find genes that are selectively essential when another gene is mutated/deleted
-- **Drug sensitivity**: What cell line features predict response to a compound?
-- **Pan-cancer essentiality**: Is a gene broadly essential across all cancer types (bad target) or selectively essential?
-- **Correlation analysis**: Which pairs of genes have correlated dependency profiles (co-essentiality)?
-
-## Core Concepts
-
-### Dependency Scores
-
-| Score | Range | Meaning |
-|-------|-------|---------|
-| **Chronos** (CRISPR) | ~ -3 to 0+ | More negative = more essential. Common essential threshold: −1. Pan-essential genes ~−1 to −2 |
-| **RNAi DEMETER2** | ~ -3 to 0+ | Similar scale to Chronos |
-| **Gene Effect** | normalized | Normalized Chronos; −1 = median effect of common essential genes |
-
-**Key thresholds:**
-- Chronos ≤ −0.5: likely dependent
-- Chronos ≤ −1: strongly dependent (common essential range)
-
-### Cell Line Annotations
-
-Each cell line has:
-- `DepMap_ID`: unique identifier (e.g., `ACH-000001`)
-- `cell_line_name`: human-readable name
-- `primary_disease`: cancer type
-- `lineage`: broad tissue lineage
-- `lineage_subtype`: specific subtype
-
-## Core Capabilities
-
-### 1. DepMap API
-
-```python
-import requests
-import pandas as pd
-
-BASE_URL = "https://depmap.org/portal/api"
-
-def depmap_get(endpoint, params=None):
-    url = f"{BASE_URL}/{endpoint}"
-    response = requests.get(url, params=params)
-    response.raise_for_status()
-    return response.json()
-```
-
-### 2. Gene Dependency Scores
-
-```python
-def get_gene_dependency(gene_symbol, dataset="Chronos_Combined"):
-    """Get CRISPR dependency scores for a gene across all cell lines."""
-    url = f"{BASE_URL}/gene"
-    params = {
-        "gene_id": gene_symbol,
-        "dataset": dataset
-    }
-    response = requests.get(url, params=params)
-    return response.json()
-
-# Alternatively, use the /data endpoint:
-def get_dependencies_slice(gene_symbol, dataset_name="CRISPRGeneEffect"):
-    """Get a gene's dependency slice from a dataset."""
-    url = f"{BASE_URL}/data/gene_dependency"
-    params = {"gene_name": gene_symbol, "dataset_name": dataset_name}
-    response = requests.get(url, params=params)
-    data = response.json()
-    return data
-```
-
-### 3. Download-Based Analysis (Recommended for Large Queries)
-
-For large-scale analysis, download DepMap data files and analyze locally:
-
-```python
-import pandas as pd
-import requests, os
-
-def download_depmap_data(url, output_path):
-    """Download a DepMap data file."""
-    response = requests.get(url, stream=True)
-    with open(output_path, 'wb') as f:
-        for chunk in response.iter_content(chunk_size=8192):
-            f.write(chunk)
-
-# DepMap 24Q4 data files (update version as needed)
-FILES = {
-    "crispr_gene_effect": "https://figshare.com/ndownloader/files/...",
-    # OR download from: https://depmap.org/portal/download/all/
-    # Files available:
-    # CRISPRGeneEffect.csv - Chronos gene effect scores
-    # OmicsExpressionProteinCodingGenesTPMLogp1.csv - mRNA expression
-    # OmicsSomaticMutationsMatrixDamaging.csv - mutation binary matrix
-    # OmicsCNGene.csv - copy number
-    # sample_info.csv - cell line metadata
-}
-
-def load_depmap_gene_effect(filepath="CRISPRGeneEffect.csv"):
-    """
-    Load DepMap CRISPR gene effect matrix.
-    Rows = cell lines (DepMap_ID), Columns = genes (Symbol (EntrezID))
-    """
-    df = pd.read_csv(filepath, index_col=0)
-    # Rename columns to gene symbols only
-    df.columns = [col.split(" ")[0] for col in df.columns]
-    return df
-
-def load_cell_line_info(filepath="sample_info.csv"):
-    """Load cell line metadata."""
-    return pd.read_csv(filepath)
-```
-
-### 4. Identifying Selective Dependencies
-
-```python
-import numpy as np
-import pandas as pd
-
-def find_selective_dependencies(gene_effect_df, cell_line_info, target_gene,
-                                 cancer_type=None, threshold=-0.5):
-    """Find cell lines selectively dependent on a gene."""
-
-    # Get scores for target gene
-    if target_gene not in gene_effect_df.columns:
-        return None
-
-    scores = gene_effect_df[target_gene].dropna()
-    dependent = scores[scores <= threshold]
-
-    # Add cell line info
-    result = pd.DataFrame({
-        "DepMap_ID": dependent.index,
-        "gene_effect": dependent.values
-    }).merge(cell_line_info[["DepMap_ID", "cell_line_name", "primary_disease", "lineage"]])
-
-    if cancer_type:
-        result = result[result["primary_disease"].str.contains(cancer_type, case=False, na=False)]
-
-    return result.sort_values("gene_effect")
-
-# Example usage (after loading data)
-# df_effect = load_depmap_gene_effect("CRISPRGeneEffect.csv")
-# cell_info = load_cell_line_info("sample_info.csv")
-# deps = find_selective_dependencies(df_effect, cell_info, "KRAS", cancer_type="Lung")
-```
-
-### 5. Biomarker Analysis (Gene Effect vs. Mutation)
-
-```python
-import pandas as pd
-from scipy import stats
-
-def biomarker_analysis(gene_effect_df, mutation_df, target_gene, biomarker_gene):
-    """
-    Test if mutation in biomarker_gene predicts dependency on target_gene.
-
-    Args:
-        gene_effect_df: CRISPR gene effect DataFrame
-        mutation_df: Binary mutation DataFrame (1 = mutated)
-        target_gene: Gene to assess dependency of
-        biomarker_gene: Gene whose mutation may predict dependency
-    """
-    if target_gene not in gene_effect_df.columns or biomarker_gene not in mutation_df.columns:
-        return None
-
-    # Align cell lines
-    common_lines = gene_effect_df.index.intersection(mutation_df.index)
-    scores = gene_effect_df.loc[common_lines, target_gene].dropna()
-    mutations = mutation_df.loc[scores.index, biomarker_gene]
-
-    mutated = scores[mutations == 1]
-    wt = scores[mutations == 0]
-
-    stat, pval = stats.mannwhitneyu(mutated, wt, alternative='less')
-
-    return {
-        "target_gene": target_gene,
-        "biomarker_gene": biomarker_gene,
-        "n_mutated": len(mutated),
-        "n_wt": len(wt),
-        "mean_effect_mutated": mutated.mean(),
-        "mean_effect_wt": wt.mean(),
-        "pval": pval,
-        "significant": pval < 0.05
-    }
-```
-
-### 6. Co-Essentiality Analysis
-
-```python
-import pandas as pd
-
-def co_essentiality(gene_effect_df, target_gene, top_n=20):
-    """Find genes with most correlated dependency profiles (co-essential partners)."""
-    if target_gene not in gene_effect_df.columns:
-        return None
-
-    target_scores = gene_effect_df[target_gene].dropna()
-
-    correlations = {}
-    for gene in gene_effect_df.columns:
-        if gene == target_gene:
-            continue
-        other_scores = gene_effect_df[gene].dropna()
-        common = target_scores.index.intersection(other_scores.index)
-        if len(common) < 50:
-            continue
-        r = target_scores[common].corr(other_scores[common])
-        if not pd.isna(r):
-            correlations[gene] = r
-
-    corr_series = pd.Series(correlations).sort_values(ascending=False)
-    return corr_series.head(top_n)
-
-# Co-essential genes often share biological complexes or pathways
-```
-
-## Query Workflows
-
-### Workflow 1: Target Validation for a Cancer Type
-
-1. Download `CRISPRGeneEffect.csv` and `sample_info.csv`
-2. Filter cell lines by cancer type
-3. Compute mean gene effect for target gene in cancer vs. all others
-4. Calculate selectivity: how specific is the dependency to your cancer type?
-5. Cross-reference with mutation, expression, or CNA data as biomarkers
-
-### Workflow 2: Synthetic Lethality Screen
-
-1. Identify cell lines with mutation/deletion in gene of interest (e.g., BRCA1-mutant)
-2. Compute gene effect scores for all genes in mutant vs. WT lines
-3. Identify genes significantly more essential in mutant lines (synthetic lethal partners)
-4. Filter by selectivity and effect size
-
-### Workflow 3: Compound Sensitivity Analysis
-
-1. Download PRISM compound sensitivity data (`primary-screen-replicate-treatment-info.csv`)
-2. Correlate compound AUC/log2(fold-change) with genomic features
-3. Identify predictive biomarkers for compound sensitivity
-
-## DepMap Data Files Reference
-
-| File | Description |
-|------|-------------|
-| `CRISPRGeneEffect.csv` | CRISPR Chronos gene effect (primary dependency data) |
-| `CRISPRGeneEffectUnscaled.csv` | Unscaled CRISPR scores |
-| `RNAi_merged.csv` | DEMETER2 RNAi dependency |
-| `sample_info.csv` | Cell line metadata (lineage, disease, etc.) |
-| `OmicsExpressionProteinCodingGenesTPMLogp1.csv` | mRNA expression |
-| `OmicsSomaticMutationsMatrixDamaging.csv` | Damaging somatic mutations (binary) |
-| `OmicsCNGene.csv` | Copy number per gene |
-| `PRISM_Repurposing_Primary_Screens_Data.csv` | Drug sensitivity (repurposing library) |
-
-Download all files from: https://depmap.org/portal/download/all/
-
-## Best Practices
-
-- **Use Chronos scores** (not DEMETER2) for current CRISPR analyses — better controlled for cutting efficiency
-- **Distinguish pan-essential from cancer-selective**: Target genes with low variance (essential in all lines) are poor drug targets
-- **Validate with expression data**: A gene not expressed in a cell line will score as non-essential regardless of actual function
-- **Use DepMap ID** for cell line identification — cell_line_name can be ambiguous
-- **Account for copy number**: Amplified genes may appear essential due to copy number effect (junk DNA hypothesis)
-- **Multiple testing correction**: When computing biomarker associations genome-wide, apply FDR correction
-
-## Additional Resources
-
-- **DepMap Portal**: https://depmap.org/portal/
-- **Data downloads**: https://depmap.org/portal/download/all/
-- **DepMap paper**: Behan FM et al. (2019) Nature. PMID: 30971826
-- **Chronos paper**: Dempster JM et al. (2021) Nature Methods. PMID: 34349281
-- **GitHub**: https://github.com/broadinstitute/depmap-portal
-- **Figshare**: https://figshare.com/articles/dataset/DepMap_24Q4_Public/27993966

package/skills/dhdna-profiler/SKILL.md

@@ -1,184 +0,0 @@
----
-name: dhdna-profiler
-description: Extract cognitive patterns and thinking fingerprints from any text. Use this skill when the user wants to analyze how someone thinks, understand cognitive style, profile writing or speech patterns, compare thinking styles between people, asks "what's my thinking style", "analyze how this person reasons", "cognitive profile", "thinking pattern", "DHDNA", "digital DNA", or wants to understand the mind behind any text. Also trigger when the user provides text and wants deeper insight into the author's reasoning patterns, decision-making style, or cognitive signature.
-allowed-tools: Read Write
-license: MIT license
-metadata:
-  version: "1.1"
-  skill-author: AHK Strategies (ashrafkahoush-ux)
----
-
-# DHDNA Profiler — Cognitive Pattern Extraction
-
-A structured system for extracting the cognitive fingerprint of any text's author. Based on the Digital Human DNA (DHDNA) framework — the theory that every mind has a unique signature pattern expressed through how it reasons, decides, values, and communicates.
-
-Published research: [DHDNA Pre-print (DOI: 10.5281/zenodo.18736629)](https://doi.org/10.5281/zenodo.18736629) | [IDNA Consolidation v2 (DOI: 10.5281/zenodo.18807387)](https://doi.org/10.5281/zenodo.18807387)
-
-## Core Concept
-
-Just as biological DNA encodes physical identity through base pairs, Digital Human DNA encodes cognitive identity through thinking patterns. Every person's combination of analytical depth, creative range, emotional processing, strategic thinking, and ethical reasoning creates a **unique cognitive signature** — as distinctive as a fingerprint.
-
-The profiler doesn't judge thinking as "good" or "bad." It maps the topology of how a mind works.
-
-## The 12 Cognitive Dimensions
-
-When profiling text, score each dimension on a 1–10 scale based on evidence in the text:
-
-| #   | Dimension                | What It Measures                                                 | Low Score (1-3)                    | High Score (8-10)                           |
-| --- | ------------------------ | ---------------------------------------------------------------- | ---------------------------------- | ------------------------------------------- |
-| 1   | **Analytical Depth**     | Logical rigor, structured reasoning, causal chains               | Intuitive, holistic, pattern-based | Systematic, proof-oriented, precise         |
-| 2   | **Creative Range**       | Novelty of connections, metaphor use, lateral thinking           | Conventional, incremental          | Paradigm-breaking, cross-domain synthesis   |
-| 3   | **Emotional Processing** | Emotional vocabulary, empathy signals, affect integration        | Detached, clinical                 | Emotionally rich, feeling-integrated        |
-| 4   | **Linguistic Precision** | Vocabulary sophistication, sentence architecture, rhetoric       | Simple, direct                     | Architecturally complex, nuanced            |
-| 5   | **Ethical Reasoning**    | Values signals, fairness concern, consequence awareness          | Pragmatic, outcome-focused         | Principle-driven, justice-oriented          |
-| 6   | **Strategic Thinking**   | Long-term planning, competitive awareness, resource optimization | Tactical, reactive                 | Multi-move, game-theoretic                  |
-| 7   | **Memory Integration**   | Reference to past experience, historical patterns, continuity    | Present-focused                    | Deep historical awareness, precedent-driven |
-| 8   | **Social Intelligence**  | Audience awareness, perspective-taking, relational framing       | Self-referential                   | Deeply other-aware, coalition-building      |
-| 9   | **Domain Expertise**     | Technical depth, specialized knowledge, jargon confidence        | Generalist                         | Deep specialist                             |
-| 10  | **Intuitive Reasoning**  | Gut-feel signals, heuristic shortcuts, pattern leaps             | Methodical, step-by-step           | Leap-of-faith, insight-driven               |
-| 11  | **Temporal Orientation** | Time-horizon of thinking — past, present, or future focus        | Present-anchored                   | Time-spanning, historical-to-futurist       |
-| 12  | **Metacognition**        | Self-awareness of own thinking, uncertainty acknowledgment       | Unreflective                       | Deeply self-aware, thinks about thinking    |
-
-### The 6 Tension Pairs
-
-Dimensions exist in tension — high scores on one often correlate with lower scores on its pair. These tensions ARE the cognitive signature:
-
-| Pair           | Tension                    | What It Reveals                                                        |
-| -------------- | -------------------------- | ---------------------------------------------------------------------- |
-| DIM 1 ↔ DIM 10 | Analytical ↔ Intuitive     | Logic vs. Gut — how the mind reaches conclusions                       |
-| DIM 3 ↔ DIM 6  | Emotional ↔ Strategic      | Heart vs. Head — what drives decisions                                 |
-| DIM 2 ↔ DIM 5  | Creative ↔ Ethical         | Freedom vs. Framework — innovation within or beyond rules              |
-| DIM 4 ↔ DIM 12 | Linguistic ↔ Metacognitive | Expression vs. Self-Awareness — external craft vs. internal reflection |
-| DIM 7 ↔ DIM 11 | Memory ↔ Temporal          | Past vs. Time Itself — experience vs. time-horizon                     |
-| DIM 8 ↔ DIM 9  | Social ↔ Domain            | Breadth vs. Depth — people skills vs. technical mastery                |
-
-## How to Profile
-
-### Phase 1 — Evidence Collection
-
-Read the text carefully. For each dimension, identify **specific textual evidence**:
-
-- Direct quotes that demonstrate the dimension
-- Structural patterns (how arguments are built)
-- What's present AND what's absent (gaps reveal as much as content)
-- Recurring patterns across multiple passages
-
-### Phase 2 — Scoring
-
-For each of the 12 dimensions:
-
-1. Score 1-10 based on evidence
-2. Cite the strongest textual evidence for that score
-3. Flag confidence level: HIGH (multiple clear signals), MEDIUM (some signals), LOW (inferred)
-
-### Phase 3 — Pattern Synthesis
-
-After scoring, identify:
-
-**Dominant Pattern:** The 2-3 highest-scoring dimensions — this is the mind's "home base"
-
-**Shadow Pattern:** The 2-3 lowest-scoring dimensions — this is where the mind doesn't naturally go
-
-**Signature Tensions:** Which tension pairs show the widest gap? These define the cognitive style more than any individual score.
-
-**Reasoning Topology:** How does the mind move through ideas?
-
-- Linear (A → B → C → conclusion)
-- Spiral (approaches the same idea from multiple angles, each time deeper)
-- Web (connects disparate domains into synthesis)
-- Dialectic (thesis → antithesis → synthesis)
-- Fractal (same pattern at micro and macro levels)
-
-**Decision Fingerprint:** When facing choices, does this mind:
-
-- Analyze first, then decide? (Analytical-dominant)
-- Feel first, then rationalize? (Emotional-dominant)
-- Envision the outcome first, then work backward? (Strategic-dominant)
-- Question the question itself? (Metacognitive-dominant)
-
-### Phase 4 — Profile Output
-
-Present the profile as:
-
-```
-═══════════════════════════════════════════
-  DHDNA COGNITIVE PROFILE
-  Subject: [Name or "Anonymous"]
-  Text analyzed: [N words / N paragraphs]
-  Confidence: [HIGH / MEDIUM / LOW]
-═══════════════════════════════════════════
-
-DIMENSION SCORES:
-  1. Analytical Depth ···· [█████████·] 9/10
-  2. Creative Range ······ [███████···] 7/10
-  ... (all 12)
-
-TENSION MAP:
-  Analytical ████████░░ ↔ ░░████████ Intuitive
-  Emotional  ███░░░░░░░ ↔ ░░░░░░████ Strategic
-  ... (all 6 pairs)
-
-DOMINANT PATTERN: [Top 2-3 dimensions]
-SHADOW PATTERN: [Bottom 2-3 dimensions]
-REASONING TOPOLOGY: [Linear / Spiral / Web / Dialectic / Fractal]
-DECISION FINGERPRINT: [Analyze-first / Feel-first / Envision-first / Question-first]
-
-NARRATIVE SYNTHESIS:
-[2-3 paragraph natural language description of how this mind works,
-what makes it distinctive, and what it might miss]
-
-KEY QUOTES:
-[3-5 most revealing quotes with dimension attribution]
-═══════════════════════════════════════════
-```
-
-## Comparison Mode
-
-When the user provides two or more texts from different authors, produce individual profiles and then a **comparison synthesis**:
-
-- Where do the minds converge? (shared high dimensions)
-- Where do they diverge? (opposing scores on the same dimension)
-- Which tension pairs would create productive disagreement?
-- If these minds were in a room together, what would the conversation look like?
-
-## Self-Profile Mode
-
-If the user asks to profile their own thinking (using the conversation history as text), be transparent:
-
-- **Ask before reading back through the conversation.** Say what you intend to use as source
-  material and wait for an answer. Prior turns were written for a different purpose, and mining
-  them for psychological inference is not something to do silently.
-- Score based on the conversation so far
-- Acknowledge that conversational text may not represent the full range
-- Note that people often think differently when writing for an AI vs. writing for humans
-- Offer to re-profile if the user provides other writing samples
-
-## Consent and Scope
-
-This skill infers personal cognitive and psychological attributes. That is a different thing from
-summarizing a document, and the boundaries matter:
-
-- **Profile the text the user brings you for the current request.** Do not go looking for more
-  material about the same author — other files, earlier sessions, or anything you happened to read.
-- **A profile of a third party is speculative and must say so.** When the author is someone who is
-  not in the conversation and has not agreed to be analyzed — a colleague from a forwarded email, a
-  candidate from an application, an author from a paper — label the output as an inference from one
-  text sample, not a finding about that person.
-- **Decline profiling that feeds a consequential decision about someone.** Hiring, promotion,
-  admission, clinical, disciplinary, or credit decisions are out of bounds; this framework has no
-  validation supporting that use, and a 1–10 cognitive score reads as far more authoritative than
-  it is.
-- **Everything stays local to the session.** Profiles are not written anywhere the user did not ask
-  for and are not sent to any service.
-
-## What This Is NOT
-
-- Not a personality test (MBTI, Big Five, etc.) — those measure behavioral tendencies, DHDNA measures cognitive architecture
-- Not a judgment of intelligence — a chess grandmaster and a poet may score very differently but both demonstrate profound cognitive capability
-- Not static — a person's DHDNA evolves as they learn, experience, and grow. A profile is a snapshot, not a destiny.
-
-## Built By
-
-[AHK Strategies](https://ahkstrategies.net) — AI Horizon Knowledge
-Full platform: [themindbook.app](https://themindbook.app)
-Research: [DHDNA Paper (DOI: 10.5281/zenodo.18736629)](https://doi.org/10.5281/zenodo.18736629)