celltype-cli 0.1.0__py3-none-any.whl

ct/ui/suggestions.py

@@ -0,0 +1,567 @@
+"""
+Ghost-text suggestions for the ct interactive terminal.
+
+500 diverse research queries spanning every domain ct supports:
+target validation, genetics, chemistry, safety, clinical, omics,
+structure, networks, repurposing, biomarkers, experimental design, etc.
+
+Shuffled at session start so every session feels different.
+"""
+
+DEFAULT_SUGGESTIONS = [
+    # ── Target validation & genetic evidence ──────────────────────
+    "what are the most genetically supported targets for AML?",
+    "is TP53 a viable drug target? check safety, selectivity, and literature",
+    "what are the co-essential partners of BRAF in melanoma?",
+    "which cancer types show the strongest BRCA1 dependency?",
+    "find GWAS evidence linking JAK2 to myeloproliferative diseases",
+    "what's the genetic evidence for PCSK9 as a cardiovascular target?",
+    "run Mendelian randomization for IL-6 in rheumatoid arthritis",
+    "which transcription factors drive EMT in pancreatic cancer?",
+    "validate KRAS as a target — GWAS, eQTL, and DepMap evidence",
+    "what genes are co-essential with CDK4 across all cancer types?",
+    "is PTPN22 a good target for autoimmune diseases? check genetic evidence",
+    "find the top 10 genetically validated targets for type 2 diabetes",
+    "what's the druggability score for the STING pathway?",
+    "which kinases have the strongest dependency in glioblastoma?",
+    "assess USP7 as a therapeutic target — expression, dependency, safety",
+    "what targets are synthetically lethal with SMAD4 loss?",
+    "find genetically supported targets for Crohn's disease",
+    "is RIPK1 a good target for neuroinflammation?",
+    "which GPCRs show tumor-specific overexpression?",
+    "evaluate EZH2 as a target in diffuse large B-cell lymphoma",
+    "what's the dependency profile of WRN in MSI-high tumors?",
+    "find top essential genes in triple-negative breast cancer cell lines",
+    "assess the target tractability of TYK2 for psoriasis",
+    "which ubiquitin ligases are overexpressed in hepatocellular carcinoma?",
+    "is DDR1 a viable target in pancreatic ductal adenocarcinoma?",
+    "what are the top CRISPR dependencies in multiple myeloma?",
+    "evaluate METTL3 as an epigenetic target in AML",
+    "find targets with strong Mendelian randomization evidence for lupus",
+    "which deubiquitinases are essential in colorectal cancer?",
+    "assess KAT6A as an oncology target — expression and dependency data",
+    "what targets emerge from GWAS for atopic dermatitis?",
+    "is CD47 a safe target? check expression across normal tissues",
+    "find co-essential gene pairs for MYC in neuroblastoma",
+    "validate PRMT5 as a target in glioma — dependency, expression, safety",
+    "which phosphatases are essential in prostate cancer?",
+    "what's the genetic evidence linking LRRK2 to Parkinson's disease?",
+    "evaluate SHP2 (PTPN11) as a target in RAS-driven cancers",
+    "find the strongest genetic associations for inflammatory bowel disease targets",
+    "is GLS1 a good target in renal cell carcinoma?",
+    "assess the druggability of the Hippo pathway component YAP1",
+
+    # ── Chemistry & compound profiling ────────────────────────────
+    "find structurally similar compounds to imatinib and compare SAR",
+    "suggest modifications to improve the selectivity of sotorasib",
+    "what's the ADMET profile of lenalidomide?",
+    "scaffold hop from erlotinib — find novel EGFR chemotypes",
+    "compare molecular descriptors of approved PROTAC degraders",
+    "run retrosynthesis for a bespoke KRASG12C covalent inhibitor",
+    "find all approved drugs with a benzimidazole scaffold",
+    "what's the SAR around the pyrimidine core of dabrafenib?",
+    "compare physicochemical properties of SGLT2 inhibitors",
+    "search ChEMBL for JAK1-selective compounds with IC50 < 10 nM",
+    "find matched molecular pairs for improving the solubility of sorafenib",
+    "what's the pharmacophore model for CDK4/6 inhibitors?",
+    "profile the chemical space of FDA-approved kinase inhibitors",
+    "suggest linker modifications for a BRD4-targeting PROTAC",
+    "compare the selectivity profiles of BTK inhibitors ibrutinib vs acalabrutinib",
+    "find PubChem compounds similar to olaparib with better oral bioavailability",
+    "what molecular features distinguish PDE4 vs PDE5 inhibitors?",
+    "analyze the SAR of HDAC inhibitors — what drives class selectivity?",
+    "run retrosynthesis planning for a novel STING agonist scaffold",
+    "find compounds in ChEMBL active against IDH1 R132H mutant",
+    "compare molecular descriptors of approved GLP-1 receptor agonist small molecules",
+    "what structural modifications improve blood-brain barrier penetration?",
+    "scaffold hop from venetoclax — find alternative BCL-2 chemotypes",
+    "search for covalent warheads suitable for targeting KRASG12C",
+    "what's the chemical diversity of approved proteasome inhibitors?",
+    "find bioisosteric replacements for the morpholine group in PI3K inhibitors",
+    "compare the 3D shape similarity of MEK inhibitors",
+    "what functional groups drive hERG channel liability?",
+    "profile the lead-likeness of top hits from a recent VEGFR2 screen",
+    "find molecular glue degraders similar to thalidomide in ChEMBL",
+    "analyze structure-activity for Aurora kinase inhibitors",
+    "what's the optimal logP range for CNS-penetrant compounds?",
+    "compare the fragment hits from FBDD campaigns against BRD4",
+    "suggest prodrug strategies to improve oral absorption of remdesivir",
+    "find all approved drugs containing a fluorinated aromatic ring",
+    "profile the chemical space of macrocyclic peptide drugs",
+    "what structural alerts should I watch for in an FGFR inhibitor program?",
+    "find ChEMBL compounds selective for CDK9 over CDK2",
+    "analyze the SAR around the indole core of sunitinib",
+    "compare approved ALK inhibitors — selectivity, potency, resistance profiles",
+
+    # ── Synergy & combinations ────────────────────────────────────
+    "find synergy partners for venetoclax in acute myeloid leukemia",
+    "predict synthetic lethality partners for ARID1A-mutant tumors",
+    "which compounds synergize with PARP inhibitors in BRCA-wild-type?",
+    "find combination partners for anti-PD-1 therapy in melanoma",
+    "predict synergy between trametinib and a CDK4/6 inhibitor in KRAS-mutant NSCLC",
+    "which metabolic vulnerabilities are exposed by MYC amplification?",
+    "find synthetic lethal interactions with PTEN loss in prostate cancer",
+    "predict combination synergy for osimertinib + MET inhibitor",
+    "which epigenetic drugs synergize with immune checkpoint inhibitors?",
+    "find combination partners for BET inhibitors in diffuse large B-cell lymphoma",
+    "predict synthetic lethality partners for CDKN2A-deleted tumors",
+    "which drugs synergize with azacitidine in myelodysplastic syndromes?",
+    "find metabolic combination opportunities in IDH1-mutant glioma",
+    "predict synergy for a KRASG12C inhibitor + SHP2 inhibitor combination",
+    "which compounds enhance sensitivity to cisplatin in ovarian cancer?",
+    "find synthetic lethal partners for STK11/LKB1 loss in lung cancer",
+    "predict the best combination partner for an FGFR inhibitor in bladder cancer",
+    "which drugs overcome resistance to venetoclax in CLL?",
+    "find synergy between HDAC inhibitors and proteasome inhibitors in myeloma",
+    "predict combination opportunities for targeting the DDR pathway in BRCA-mutant tumors",
+
+    # ── Clinical & competitive intelligence ───────────────────────
+    "compare dose-response of doxorubicin across breast vs lung cell lines",
+    "which kinase inhibitors show the best therapeutic window in solid tumors?",
+    "search PubMed for KRAS G12C inhibitors in clinical trials",
+    "what's the competitive landscape for GLP-1 receptor agonists?",
+    "estimate patient population for FGFR2 fusion cholangiocarcinoma",
+    "find clinical trials testing bispecific antibodies in solid tumors",
+    "what's the clinical pipeline for TEAD inhibitors?",
+    "estimate patient stratification for BRCA1/2-mutant ovarian cancer",
+    "find clinical trials for CLDN18.2-targeting agents in gastric cancer",
+    "what's the competitive landscape for anti-TIGIT antibodies?",
+    "compare approved CDK4/6 inhibitors — efficacy, toxicity, market share",
+    "estimate the addressable population for NTRK fusion-positive cancers",
+    "find Phase III trials for ADCs in breast cancer",
+    "what's the clinical development status of KRAS inhibitors?",
+    "compare therapeutic windows of taxanes across solid tumor types",
+    "search for clinical trials combining immunotherapy + TKIs in RCC",
+    "what's the latest competitive landscape for NASH/MASH therapies?",
+    "estimate patient population for HER2-low breast cancer",
+    "find clinical trials testing CAR-T cells in solid tumors",
+    "what drugs are in clinical development for sickle cell disease?",
+    "compare the clinical efficacy of JAK inhibitors in atopic dermatitis",
+    "what's the competitive landscape for oral PCSK9 inhibitors?",
+    "find Phase II+ trials for degraders/PROTACs in oncology",
+    "estimate the addressable market for EGFR exon 20 insertion mutations",
+    "what's the clinical pipeline for tau-targeting therapies in Alzheimer's?",
+    "compare dose-response curves for VEGFR inhibitors in renal cell lines",
+    "find trials testing combination of PARP inhibitor + anti-PD-L1",
+    "what's the competitive landscape for bispecific T-cell engagers?",
+    "estimate patient stratification for MSI-high solid tumors",
+    "search for clinical trials using CRISPR-based therapies",
+
+    # ── Safety & off-target ───────────────────────────────────────
+    "profile the safety and off-target risks of CDK4/6 inhibitors",
+    "what mutations confer resistance to EGFR inhibitors?",
+    "check SALL4 degradation risk for new thalidomide analogs",
+    "predict drug-drug interactions for venetoclax + azacitidine",
+    "what's the antitarget profile of a pan-BET inhibitor?",
+    "predict ADMET properties for a novel STING agonist",
+    "which off-targets should I worry about for a CDK9 inhibitor?",
+    "assess hERG liability of approved kinase inhibitors",
+    "what's the safety profile of HDAC inhibitors in the clinic?",
+    "predict hepatotoxicity risk for a novel FGFR inhibitor scaffold",
+    "what are common resistance mechanisms to ALK inhibitors?",
+    "check if my compound series has PAINS structural alerts",
+    "profile the safety margins of approved BTK inhibitors",
+    "predict potential DDIs for an oral SERD in breast cancer",
+    "what off-target kinases does dasatinib hit?",
+    "assess the cardiovascular safety of JAK inhibitors",
+    "what resistance mutations emerge under osimertinib treatment?",
+    "predict CYP3A4 inhibition potential for a macrocyclic compound",
+    "what's the therapeutic index of doxorubicin across tissue types?",
+    "find known idiosyncratic toxicities of approved proteasome inhibitors",
+    "check for neosubstrate degradation risk with a cereblon-binding compound",
+    "predict genotoxicity flags for a novel covalent inhibitor",
+    "what safety signals emerged in post-marketing for checkpoint inhibitors?",
+    "assess the renal toxicity potential of a platinum-based analog",
+    "predict DDI risk for combining a CYP2D6 substrate with fluoxetine",
+
+    # ── Omics & expression ────────────────────────────────────────
+    "run pathway enrichment on MYC-dependent gene expression signatures",
+    "find single-cell datasets for tumor-infiltrating lymphocytes",
+    "what genes are differentially expressed in KRAS-mutant vs wild-type NSCLC?",
+    "search GEO for RNA-seq datasets in Alzheimer's disease",
+    "deconvolve immune cell types from TCGA breast cancer bulk RNA-seq",
+    "find L1000 signatures most similar to CDK4/6 inhibitor treatment",
+    "what pathways are enriched in MYC-amplified neuroblastoma?",
+    "search CellxGene for single-cell atlases of human liver",
+    "run differential expression analysis for TP53-mutant vs wild-type AML",
+    "find transcription factor activity signatures in EMT",
+    "what immune subtypes exist in TCGA melanoma samples?",
+    "search GEO for ATAC-seq datasets in hematopoietic stem cells",
+    "find gene expression signatures that predict response to immunotherapy",
+    "analyze pathway enrichment for genes co-expressed with VEGFA",
+    "deconvolve tumor microenvironment from TCGA pancreatic cancer data",
+    "find L1000 compounds that reverse an inflammatory gene signature",
+    "search CellxGene for single-cell data on human kidney organoids",
+    "what genes are upregulated in drug-resistant melanoma?",
+    "run immune scoring on TCGA lung adenocarcinoma cohort",
+    "find methylation differences between normal and tumor colon tissue",
+    "search for proteomics datasets comparing primary vs metastatic tumors",
+    "analyze chromatin accessibility in T-cell exhaustion",
+    "find spatial transcriptomics datasets for human brain tumors",
+    "what gene sets are enriched in oxidative phosphorylation-dependent cancers?",
+    "search GEO for ChIP-seq data on EZH2 in lymphoma",
+    "deconvolve cell types from bulk RNA-seq of rheumatoid arthritis synovium",
+    "find datasets profiling response to CAR-T cell therapy",
+    "run pathway enrichment on genes differentially methylated in glioblastoma",
+    "search for multi-omics integration datasets in breast cancer",
+    "what expression patterns distinguish luminal A from luminal B breast cancer?",
+
+    # ── Structure & docking ───────────────────────────────────────
+    "fetch the AlphaFold structure for human NLRP3 and find binding sites",
+    "dock metformin into the AMPK binding pocket",
+    "predict ternary complex for a VHL-based PROTAC targeting BRD4",
+    "find allosteric binding sites on KRASG12C from PDB structures",
+    "fetch the crystal structure of EGFR T790M and map resistance mutations",
+    "dock a novel compound into the CDK2 ATP binding site",
+    "predict binding mode for a STING agonist in the ligand pocket",
+    "find PDB structures for ROR-gamma with bound inverse agonists",
+    "compare binding sites of CDK4 vs CDK6 for selective inhibitor design",
+    "fetch the AlphaFold structure for GPR75 and identify druggable pockets",
+    "dock ibrutinib into the BTK active site and identify key interactions",
+    "predict the ternary complex for a CRBN-based PROTAC targeting GSPT1",
+    "find co-crystal structures of BRD4 with different chemotypes",
+    "map the binding site residues of PCSK9 that interact with LDLR",
+    "compare the pocket volumes of different GPCR family members",
+    "fetch the cryo-EM structure of the CFTR channel",
+    "identify cryptic binding sites on the surface of IL-17A",
+    "dock osimertinib into EGFR C797S mutant — does it still bind?",
+    "find PDB structures for PRMT5 and identify substrate binding pockets",
+    "predict binding pose of a molecular glue in the CRBN-substrate interface",
+
+    # ── Protein & network analysis ────────────────────────────────
+    "what are the protein-protein interaction partners of p53?",
+    "map the pathway crosstalk between PI3K/AKT and MAPK signaling",
+    "annotate functional domains of the CFTR protein",
+    "find all proteins that interact with MDM2 in the STRING network",
+    "map the EGFR signaling network and identify key nodes",
+    "annotate the domain architecture of the BRCA1 protein",
+    "what proteins form a complex with SMAD4?",
+    "find pathway crosstalk between WNT and Notch signaling",
+    "compute ESM-2 embeddings for KRAS wild-type and G12C mutant",
+    "identify hub proteins in the DNA damage response network",
+    "map the interactome of the PRC2 complex",
+    "what are the functional domains of ALK and where do resistance mutations cluster?",
+    "find all known substrates of the CRL4-CRBN E3 ligase complex",
+    "analyze the protein interaction network around NF-kB signaling",
+    "compute protein embeddings to find functional analogs of BCL-2",
+    "what proteins interact with both p53 and MDM4?",
+    "map the ubiquitin-proteasome pathway network in cancer",
+    "identify regulatory nodes in the mTOR signaling pathway",
+    "annotate post-translational modifications on the histone H3 protein",
+    "find the protein-protein interaction interface of PD-1 and PD-L1",
+
+    # ── Repurposing & literature ──────────────────────────────────
+    "find drug repurposing candidates for inflammatory bowel disease",
+    "search recent patents on PD-L1 small molecule inhibitors",
+    "what does the literature say about senolytics in idiopathic pulmonary fibrosis?",
+    "find CMap connections for repurposing approved drugs to AML",
+    "search PubMed for CRISPR screens identifying new cancer dependencies",
+    "what are the latest repurposing hypotheses for metformin in cancer?",
+    "find patent filings for molecular glue degraders in the last 2 years",
+    "search OpenAlex for review articles on targeted protein degradation",
+    "what approved drugs could be repurposed for Huntington's disease?",
+    "find publications on resistance to KRASG12C inhibitors",
+    "search PubMed for AI-driven drug discovery success stories",
+    "find CMap compounds that mimic the effect of PTEN restoration",
+    "search patent landscape for ADC linker-payload innovations",
+    "what does the literature say about ferroptosis as a cancer vulnerability?",
+    "find repurposing candidates for rare pediatric cancers",
+    "search PubMed for papers linking gut microbiome to drug response",
+    "find recent reviews on PROTAC clinical development",
+    "what approved drugs show activity in senolytic screens?",
+    "search OpenAlex for publications on spatial transcriptomics methods",
+    "find patent filings for bispecific antibodies in immuno-oncology",
+    "what does the literature say about epigenetic therapy in MDS?",
+    "search for recent publications on CRISPR base editing therapeutics",
+    "find CMap signatures that reverse an Alzheimer's disease gene program",
+    "search PubMed for resistance mechanisms to ADCs",
+    "what repurposing opportunities exist for statins in oncology?",
+
+    # ── Biomarkers & patient stratification ───────────────────────
+    "which mutations predict sensitivity to osimertinib?",
+    "design a biomarker panel for early-stage hepatocellular carcinoma",
+    "what biomarkers predict response to anti-PD-1 therapy?",
+    "find resistance biomarkers for FGFR inhibitors in bladder cancer",
+    "design a companion diagnostic panel for CDK4/6 inhibitor therapy",
+    "which genomic alterations predict sensitivity to PARP inhibitors?",
+    "find biomarkers that distinguish MDS from de novo AML",
+    "what's the optimal biomarker strategy for a KRASG12C inhibitor trial?",
+    "identify pharmacodynamic biomarkers for EZH2 inhibitor treatment",
+    "which mutations predict resistance to second-generation ALK inhibitors?",
+    "design a liquid biopsy panel for monitoring EGFR-mutant NSCLC",
+    "find predictive biomarkers for venetoclax response in AML",
+    "what gene expression signatures predict platinum sensitivity in ovarian cancer?",
+    "identify biomarkers for patient selection in anti-TIGIT trials",
+    "which copy number alterations predict response to PI3K inhibitors?",
+    "design a mutation panel for hereditary cancer predisposition screening",
+    "find biomarkers that predict cardiotoxicity from anthracycline treatment",
+    "what biomarkers stratify responders vs non-responders to CAR-T therapy?",
+    "identify early response biomarkers for BET inhibitor treatment",
+    "which immune markers predict benefit from combination immunotherapy?",
+
+    # ── Experimental design & CRO ─────────────────────────────────
+    "design a CRO assay to test CDK9 inhibitor selectivity",
+    "estimate timeline and cost for a 384-well high-throughput screen",
+    "design a selectivity panel for a novel kinase inhibitor",
+    "what's the best assay format to measure PROTAC-induced degradation?",
+    "estimate costs for outsourcing an in vivo PK study in mice",
+    "design a cell viability assay panel for a CDK2 inhibitor",
+    "find CROs that offer CRISPR screening services",
+    "design a dose-response experiment for combination synergy testing",
+    "what assay would best measure target engagement for a STING agonist?",
+    "estimate timeline for a lead optimization campaign with medicinal chemistry CRO",
+    "design an ADME study package for a preclinical candidate",
+    "what's the right assay cascade for an allosteric kinase inhibitor program?",
+    "find CROs that offer organoid-based drug sensitivity testing",
+    "design a biomarker validation study for a companion diagnostic",
+    "estimate cost for a 1000-compound diversity screen against a novel target",
+    "what animal models are most relevant for testing NASH therapeutics?",
+    "design an ex vivo assay to test immune cell killing with a bispecific",
+    "find CROs specializing in CNS drug delivery assessment",
+    "design a screening cascade for a GPCR agonist program",
+    "estimate timeline for IND-enabling studies for a small molecule",
+
+    # ── Genomics & variants ───────────────────────────────────────
+    "find GWAS loci associated with response to statin therapy",
+    "annotate the functional impact of BRAF V600E mutation",
+    "what eQTLs regulate expression of IL6 in immune cells?",
+    "find colocalization evidence between GWAS hits and eQTLs for SLE",
+    "annotate all known pathogenic variants in the BRCA2 gene",
+    "what pharmacogenomic variants affect warfarin metabolism?",
+    "find GWAS associations for drug-induced liver injury",
+    "run variant annotation for EGFR L858R — clinical significance and frequency",
+    "what are the most common somatic mutations in cholangiocarcinoma?",
+    "find eQTL data linking genetic variants to FTO expression",
+    "annotate the functional domains affected by TP53 hotspot mutations",
+    "what GWAS loci are shared between Alzheimer's and cardiovascular disease?",
+    "find rare variants in PCSK9 associated with low LDL cholesterol",
+    "run Mendelian randomization for adiponectin levels and diabetes risk",
+    "what somatic mutations are enriched in platinum-resistant ovarian cancer?",
+    "annotate the splice variants of the androgen receptor in prostate cancer",
+    "find GWAS evidence for drug targets in major depressive disorder",
+    "what's the allele frequency of DPYD variants relevant to 5-FU toxicity?",
+    "find colocalization between IBD GWAS hits and gut tissue eQTLs",
+    "annotate all clinically actionable variants in the NTRK1/2/3 genes",
+
+    # ── Single-cell & spatial ─────────────────────────────────────
+    "cluster and annotate cell types in a PBMC single-cell dataset",
+    "find trajectory analysis of T-cell differentiation in the tumor microenvironment",
+    "search CellxGene for human lung single-cell atlases",
+    "what cell types express PD-L1 in the tumor microenvironment?",
+    "run cell type annotation on a new scRNA-seq dataset from kidney",
+    "find spatial transcriptomics data for human colorectal cancer",
+    "cluster spatial spots and identify tissue architecture in liver sections",
+    "search for single-cell datasets profiling CAR-T cell products",
+    "what cell types are enriched in the stroma of pancreatic cancer?",
+    "find scRNA-seq data comparing healthy vs fibrotic lung tissue",
+    "identify spatially co-localized cell types in breast tumor sections",
+    "search CellxGene for single-cell data on human bone marrow",
+    "run pseudotime analysis on developing B-cells from a scRNA-seq experiment",
+    "find single-cell datasets for human intestinal organoids",
+    "what are the marker genes for exhausted CD8+ T cells in single-cell data?",
+    "search for spatial proteomics datasets in melanoma",
+    "cluster and annotate a scRNA-seq dataset from human heart tissue",
+    "find single-cell multi-omics datasets combining RNA + ATAC",
+    "identify rare cell populations in a tumor single-cell dataset",
+    "search CellxGene for developmental biology single-cell atlases",
+
+    # ── Epigenomics & methylation ─────────────────────────────────
+    "find differentially methylated regions in AML vs normal hematopoietic cells",
+    "analyze chromatin accessibility at the MYC locus in lymphoma",
+    "search for ChIP-seq data on H3K27me3 in embryonic stem cells",
+    "find enhancer regions active in hepatocytes using ATAC-seq data",
+    "profile DNA methylation changes during cellular senescence",
+    "find super-enhancers driving oncogene expression in neuroblastoma",
+    "analyze histone modification patterns at the TP53 promoter in cancer",
+    "search for ATAC-seq data comparing naive vs memory T cells",
+    "what chromatin states distinguish cancer stem cells from bulk tumor?",
+    "find Hi-C data showing 3D genome organization in normal vs leukemic cells",
+    "profile methylation patterns at imprinted loci in Beckwith-Wiedemann syndrome",
+    "identify regions of chromatin remodeling during macrophage polarization",
+    "find epigenomic datasets profiling drug-resistant cancer cell lines",
+    "what histone marks define poised enhancers in human islet cells?",
+    "analyze DNA methylation age acceleration in different cancer types",
+
+    # ── Proteomics ────────────────────────────────────────────────
+    "find differentially expressed proteins in KRAS-mutant vs wild-type CRC",
+    "run pathway enrichment on proteomics data from drug-treated cells",
+    "search for phosphoproteomics datasets in EGFR-driven lung cancer",
+    "what proteins are upregulated in cisplatin-resistant ovarian cancer?",
+    "find proteomics data comparing primary tumors vs metastatic sites",
+    "identify kinase substrates altered by CDK4/6 inhibitor treatment",
+    "search for protein-protein interaction data from AP-MS experiments",
+    "what post-translational modifications change during T-cell activation?",
+    "find ubiquitinomics data for PROTAC-treated cell lines",
+    "compare protein expression across the NCI-60 cell line panel",
+
+    # ── Drug resistance ───────────────────────────────────────────
+    "what resistance mechanisms emerge under KRASG12C inhibitor treatment?",
+    "find second-site mutations that confer resistance to lorlatinib",
+    "how does tumor heterogeneity drive resistance to EGFR TKIs?",
+    "search for literature on acquired resistance to ADCs",
+    "what pathway reactivation mechanisms drive resistance to BRAF inhibitors?",
+    "find resistance mutations to BTK inhibitors in CLL",
+    "what non-genetic mechanisms contribute to resistance to targeted therapy?",
+    "search PubMed for studies on preventing resistance to CDK4/6 inhibitors",
+    "find biomarkers that predict early resistance to immunotherapy",
+    "what are the known escape mechanisms from venetoclax in AML?",
+
+    # ── Rare diseases & pediatrics ────────────────────────────────
+    "find druggable targets for spinal muscular atrophy beyond SMN",
+    "what therapies are in development for Duchenne muscular dystrophy?",
+    "search for clinical trials in pediatric high-grade glioma",
+    "find genetic targets for Rett syndrome",
+    "what's the drug development landscape for cystic fibrosis beyond CFTR modulators?",
+    "find targets for Dravet syndrome beyond SCN1A",
+    "search PubMed for gene therapy approaches in Gaucher disease",
+    "what drugs are being repurposed for Friedreich's ataxia?",
+    "find potential targets for familial Mediterranean fever",
+    "search for clinical trials in pediatric AML with novel agents",
+
+    # ── Immunology & immuno-oncology ──────────────────────────────
+    "profile the immune landscape of TCGA colorectal cancer",
+    "find expression patterns of immune checkpoints across solid tumors",
+    "what cell types infiltrate pancreatic tumors and correlate with survival?",
+    "compare immune scores across cancer types — which are immunologically 'hot'?",
+    "find literature on adenosine pathway inhibitors in immuno-oncology",
+    "what's the expression profile of LAG-3 across cancer types?",
+    "search for scRNA-seq data on myeloid-derived suppressor cells in tumors",
+    "find therapeutic targets in the tumor-associated macrophage phenotype",
+    "profile the T-cell receptor repertoire diversity in melanoma responders",
+    "what's the competitive landscape for CXCR4 antagonists in oncology?",
+    "find evidence for CD73 as an immunotherapy target",
+    "search PubMed for NK cell-based cancer immunotherapy approaches",
+    "what combinations enhance dendritic cell-mediated anti-tumor immunity?",
+    "profile cytokine networks in the tumor microenvironment of NSCLC",
+    "find targets to overcome T-cell exhaustion in chronic viral infection",
+
+    # ── Metabolism & metabolomics ─────────────────────────────────
+    "find metabolic vulnerabilities in IDH1-mutant glioma",
+    "what metabolic pathways are rewired in KRAS-driven pancreatic cancer?",
+    "search for metabolomics datasets comparing responders vs non-responders to immunotherapy",
+    "find druggable targets in the one-carbon metabolism pathway",
+    "what metabolic dependencies distinguish cancer stem cells?",
+    "profile lipid metabolism changes in steatohepatitis models",
+    "find targets in the glutamine addiction pathway of MYC-driven tumors",
+    "what metabolic biomarkers predict response to metformin?",
+    "search PubMed for ferroptosis as a therapeutic strategy in cancer",
+    "find metabolic synthetic lethality with KEAP1 loss in lung cancer",
+
+    # ── Neuroscience targets ──────────────────────────────────────
+    "find genetically validated targets for Alzheimer's disease",
+    "what's the competitive landscape for TREM2-modulating therapies?",
+    "search for clinical trials targeting alpha-synuclein in Parkinson's",
+    "find druggable targets for amyotrophic lateral sclerosis",
+    "what's the genetic evidence for GBA as a Parkinson's target?",
+    "search PubMed for tau propagation inhibitors in clinical development",
+    "find targets for treatment-resistant depression beyond monoamines",
+    "what's the BBB penetration profile of approved CNS drugs?",
+    "search for genetic associations between APOE and treatment response in AD",
+    "find novel targets for neuropathic pain beyond ion channels",
+
+    # ── Infectious disease ────────────────────────────────────────
+    "find druggable targets in the SARS-CoV-2 replication machinery",
+    "what's the competitive landscape for broad-spectrum antivirals?",
+    "search PubMed for host-directed therapies against tuberculosis",
+    "find targets for drug-resistant Gram-negative bacteria",
+    "what repurposing candidates exist for emerging viral threats?",
+    "search for clinical trials testing new antibiotics for MRSA",
+    "find potential targets in the malaria parasite life cycle",
+    "what's the latest pipeline for antifungal drugs?",
+    "search PubMed for CRISPR-based antimicrobial strategies",
+    "find host targets that broadly restrict respiratory virus replication",
+
+    # ── Fibrosis & inflammation ───────────────────────────────────
+    "find genetically supported targets for idiopathic pulmonary fibrosis",
+    "what's the competitive landscape for anti-fibrotic therapies?",
+    "search for clinical trials in systemic sclerosis with novel agents",
+    "find targets linking inflammation and fibrosis in the liver",
+    "what's the mechanism of action of nintedanib in IPF?",
+    "search PubMed for IL-11 as a fibrosis target",
+    "find biomarkers that predict fibrosis progression in NASH",
+    "what targets are emerging for cardiac fibrosis?",
+    "search for clinical trials targeting TGF-beta in fibrotic diseases",
+    "find druggable targets in the senescence-associated secretory phenotype",
+
+    # ── Cardiovascular ────────────────────────────────────────────
+    "find genetically validated targets for heart failure",
+    "what's the clinical pipeline for RNA-targeting cardiovascular therapies?",
+    "search PubMed for ANGPTL3 inhibitors in dyslipidemia",
+    "find GWAS targets for atrial fibrillation",
+    "what repurposing opportunities exist for approved drugs in heart failure?",
+    "find biomarkers for early detection of atherosclerosis",
+    "what's the competitive landscape for LP(a)-lowering therapies?",
+    "search for targets in the cardiac inflammation pathway post-MI",
+    "find genetic evidence linking CETP to cardiovascular outcomes",
+    "what novel RNA-based therapies are in development for hypercholesterolemia?",
+
+    # ── Multi-step workflows & complex queries ────────────────────
+    "profile lenalidomide end-to-end: chemistry, targets, safety, clinical positioning",
+    "validate IDH1 as a target — genetics, expression, druggability, competitive landscape",
+    "full compound profile for osimertinib: SAR, ADMET, resistance, combinations",
+    "evaluate a PROTAC approach for ER-alpha — feasibility, linker design, safety",
+    "comprehensive target assessment for METTL3 in AML — from genetics to clinical",
+    "design a lead optimization strategy for a KRASG12D inhibitor series",
+    "compare three approaches to targeting MYC: direct binding, synthetic lethality, degradation",
+    "build a biomarker strategy for an EZH2 inhibitor Phase II trial",
+    "full competitive intelligence report on CDK4/6 inhibitor market",
+    "design a drug repurposing screen for ALS using CMap and expression data",
+    "evaluate BRD4 as a PROTAC target — structure, degradability, selectivity risks",
+    "comprehensive safety assessment for a novel cereblon modulator",
+    "compare PPI network, expression, and dependency data for NFE2L2/NRF2",
+    "multi-omics integration for discovering biomarkers in triple-negative breast cancer",
+    "design an end-to-end screening cascade for a PPI inhibitor program",
+    "full landscape analysis: CLDN18.2-targeting strategies in gastric cancer",
+    "evaluate allosteric vs orthosteric approaches for targeting SHP2",
+    "build an evidence dossier for PRMT5 as an oncology target",
+    "design a clinical development plan for a first-in-class TEAD inhibitor",
+    "comprehensive analysis of the STING agonist therapeutic landscape",
+
+    # ── RNA therapeutics & gene therapy ───────────────────────────
+    "find ASO and siRNA therapies in clinical development for liver diseases",
+    "what's the competitive landscape for mRNA therapeutics beyond vaccines?",
+    "search PubMed for CRISPR gene editing approaches to sickle cell disease",
+    "find targets amenable to antisense oligonucleotide knockdown in CNS",
+    "what RNA-targeting modalities are being explored for KRAS?",
+    "search for clinical trials using AAV gene therapy in inherited retinal disease",
+    "find druggable non-coding RNAs in cancer — lncRNAs and miRNAs",
+    "what's the state of base editing therapies for genetic blood disorders?",
+    "compare delivery platforms for RNA therapeutics — LNP vs GalNAc vs exosomes",
+    "find targets for splice-switching oligonucleotides in neuromuscular diseases",
+
+    # ── Aging & longevity ─────────────────────────────────────────
+    "find druggable targets in cellular senescence pathways",
+    "what senolytics are in clinical development and for which indications?",
+    "search PubMed for rapamycin analogs in aging research",
+    "find genetic variants associated with exceptional longevity",
+    "what's the evidence for NAD+ boosters in age-related diseases?",
+    "profile the senescence-associated secretory phenotype as a drug target space",
+    "find clinical trials targeting aging biology directly",
+    "what telomere biology targets are being explored therapeutically?",
+    "search for epigenetic clock-based endpoints in clinical trials",
+    "find repurposing candidates from longevity-associated drug screens",
+
+    # ── Autoimmune & inflammatory ─────────────────────────────────
+    "find genetically supported targets for systemic lupus erythematosus",
+    "what's the competitive landscape for anti-IL-23 therapies?",
+    "search for clinical trials in giant cell arteritis with novel agents",
+    "find targets at the intersection of gut barrier integrity and autoimmunity",
+    "what's the mechanism of action of approved JAK inhibitors in RA?",
+    "compare selectivity profiles of S1P receptor modulators for MS",
+    "find biomarkers that predict response to anti-TNF therapy in IBD",
+    "search PubMed for regulatory T-cell-based therapies in autoimmunity",
+    "what targets are emerging for IgA nephropathy?",
+    "find genetic evidence linking TYK2 to multiple autoimmune diseases",
+
+    # ── Oncology — specific tumor types ───────────────────────────
+    "what are the top emerging targets in small cell lung cancer?",
+    "find actionable molecular subtypes in muscle-invasive bladder cancer",
+    "profile the molecular landscape of uveal melanoma",
+    "what targets are unique to mesothelioma vs other solid tumors?",
+    "find druggable vulnerabilities in TP53-mutant myelodysplastic syndromes",
+    "what's the molecular taxonomy of endometrial cancer subtypes?",
+    "search for novel targets in dedifferentiated liposarcoma",
+    "find the key drivers in anaplastic thyroid cancer",
+    "profile the immune and molecular landscape of Merkel cell carcinoma",
+    "what targets are being explored for desmoid tumors?",
+]