A collection of example queries demonstrating different capabilities of KG-RAG in Versa.
- Disease-Gene Associations
- Disease-Disease Intersections
- Shared Disease Symptoms
- Disease-Drug Relationships
- Disease Classification
Query Type: Single disease - gene associations
Features Demonstrated: Gene identification with evidence
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SECTION 1 - SPOKE-PRIORITIZED RESPONSE: Based on SPOKE knowledge base:
ABL1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org AANAT: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org ADH5: Associated with leukemia. Provenance: HPO BCR: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org BUB3: Associated with leukemia. Provenance: HPO CD33: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org CD38: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org CEP57: Associated with leukemia. Provenance: HPO CHIC2: Associated with leukemia. Provenance: HPO DDX41: Associated with leukemia. Provenance: HPO DNAJC21: Associated with leukemia. Provenance: HPO DYNC2LI1: Associated with leukemia. Provenance: HPO EFL1: Associated with leukemia. Provenance: HPO EGF: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org ELANE: Associated with leukemia. Provenance: HPO EVC: Associated with leukemia. Provenance: HPO F13B: Associated with leukemia. Provenance: HPO FANCC: Associated with leukemia. Provenance: HPO FANCD2: Associated with leukemia. Provenance: HPO FLT3: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org GNB1: Associated with leukemia. Provenance: HPO H4C9: Associated with leukemia. Provenance: HPO HAX1: Associated with leukemia. Provenance: HPO KIT: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org KRAS: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org LIG4: Associated with leukemia. Provenance: HPO LPP: Associated with leukemia. Provenance: HPO MBD4: Associated with leukemia. Provenance: HPO MEFV: Associated with leukemia. Provenance: HPO MEIS1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org MSH2: Associated with leukemia. Provenance: HPO MYD88: Associated with leukemia. Provenance: HPO MYH11: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org NOTCH1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org NPM1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org NRAS: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org NSD1: Associated with leukemia. Provenance: HPO NUMA1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org NUTM1: Associated with leukemia. Provenance: HPO PBX1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org PIK3CB: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org PIK3R1: Associated with leukemia. Provenance: HPO PML: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org POT1: Associated with leukemia. Provenance: HPO PXDNL: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org RARA: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org RECQL4: Associated with leukemia. Provenance: HPO RNASEH2B: Associated with leukemia. Provenance: HPO RPL27: Associated with leukemia. Provenance: HPO RPL5: Associated with leukemia. Provenance: HPO RPL26: Associated with leukemia. Provenance: HPO RPS15A: Associated with leukemia. Provenance: HPO RPS20: Associated with leukemia. Provenance: HPO RUNX1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org RUNX1T1: Associated with leukemia. Provenance: DISEASES database - https://diseases.jensenlab.org SETBP1: Associated with leukemia. Provenance: HPO SF3B1: Associated with leukemia. Provenance: HPO SH3GL1: Associated with leukemia. Provenance: HPO SMPD1: Associated with leukemia. Provenance: HPO SRP54: Associated with leukemia. Provenance: HPO TAL2: Associated with leukemia. Provenance: HPO TERT: Associated with leukemia. Provenance: HPO THPO: Associated with leukemia. Provenance: HPO TRIP13: Associated with leukemia. Provenance: HPO TREX1: Associated with leukemia. Provenance: HPO TREM2: Associated with leukemia. Provenance: HPO XRCC4: Associated with leukemia. Provenance: HPO
To provide a complete answer, I’ll add information from my trained biomedical knowledge along with this:
BRCA1/BRCA2: Mutations in these genes, commonly associated with breast cancer, have also been linked to an increased risk of leukemia. TP53: Mutations in this tumor suppressor gene are known to contribute to various cancers, including leukemia. RUNX1: Mutations in this gene are associated with familial platelet disorder with a predisposition to acute myeloid leukemia (AML).
SECTION 2 - ANALYSIS WITHOUT SPOKE (USING KNOWLEDGE FROM LLM TRAINING)
Genetic factors play a significant role in the development of leukemia. Key genes implicated include:
BRCA1/BRCA2: Known for their role in breast cancer, mutations in these genes can also increase leukemia risk. TP53: A critical tumor suppressor gene, mutations in TP53 are linked to various cancers, including leukemia. RUNX1: Mutations in this gene are associated with familial platelet disorder and predispose individuals to acute myeloid leukemia (AML). FLT3: Mutations in this gene are common in acute myeloid leukemia (AML) and are associated with poor prognosis. NPM1: Mutations in this gene are frequently found in AML and are used as a diagnostic marker.
SECTION 3 - SUMMARY
From Section 1 (with SPOKE):
SPOKE provides a comprehensive list of genes associated with leukemia, including ABL1, FLT3, RUNX1, and many others, with provenance from the HPO and DISEASES databases. Additional genes such as BRCA1/BRCA2 and TP53, which are not listed in SPOKE, are also known to be associated with leukemia based on broader biomedical knowledge.
From Section 2 (without SPOKE):
Key genetic factors for leukemia include BRCA1/BRCA2, TP53, RUNX1, FLT3, and NPM1, highlighting the importance of these genes in the disease’s pathogenesis.
Summary: Genetic factors play a crucial role in the development of leukemia. The SPOKE knowledge base identifies numerous genes associated with leukemia, supported by data from the HPO and DISEASES databases. Additionally, well-known genes such as BRCA1/BRCA2 and TP53, which are not listed in SPOKE, are also significant contributors to leukemia risk. For a comprehensive understanding, it is essential to consider both SPOKE-derived information and broader biomedical knowledge. Always consult a healthcare professional for personalized medical advice.
Query Type: Multi-disease gene intersection
Features Demonstrated: Cross-disease analysis, shared genetic factors
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SECTION 1 - SPOKE-PRIORITIZED RESPONSE: Based on SPOKE knowledge base:
APP (Amyloid Beta Precursor Protein)
Explanation: APP is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: DISEASES database - https://diseases.jensenlab.org APOE (Apolipoprotein E)
Explanation: APOE is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: DISEASES database - https://diseases.jensenlab.org MAPT (Microtubule Associated Protein Tau)
Explanation: MAPT is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: DISEASES database - https://diseases.jensenlab.org, GWAS Catalog PSEN1 (Presenilin 1)
Explanation: PSEN1 is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: DISEASES database - https://diseases.jensenlab.org SNCA (Synuclein Alpha)
Explanation: SNCA is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: DISEASES database - https://diseases.jensenlab.org, GWAS Catalog To provide a complete answer, I’ll add information from my trained biomedical knowledge along with this:
TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) Explanation: TREM2 is associated with both Parkinson’s disease and Alzheimer’s disease. Provenance: GWAS Catalog, DISEASES database - https://diseases.jensenlab.org
SECTION 2 - ANALYSIS WITHOUT SPOKE (USING KNOWLEDGE FROM LLM TRAINING):
Based on my trained biomedical knowledge, the following genes are commonly associated with both Parkinson’s disease and Alzheimer’s disease:
APP (Amyloid Beta Precursor Protein)
Explanation: APP is involved in the formation of amyloid plaques, a hallmark of Alzheimer’s disease, and has been implicated in Parkinson’s disease pathology. APOE (Apolipoprotein E)
Explanation: APOE is a major genetic risk factor for Alzheimer’s disease and has also been linked to Parkinson’s disease. MAPT (Microtubule Associated Protein Tau)
Explanation: MAPT encodes the tau protein, which forms neurofibrillary tangles in Alzheimer’s disease and is also implicated in Parkinson’s disease. PSEN1 (Presenilin 1)
Explanation: PSEN1 mutations are a known cause of early-onset Alzheimer’s disease and have been associated with Parkinson’s disease. SNCA (Synuclein Alpha)
Explanation: SNCA encodes alpha-synuclein, a protein that aggregates in both Parkinson’s disease and Alzheimer’s disease. TREM2 (Triggering Receptor Expressed on Myeloid Cells 2)
Explanation: TREM2 mutations are associated with increased risk of Alzheimer’s disease and have been implicated in Parkinson’s disease.
SECTION 3 - SUMMARY:
Summary:
SPOKE Information:
Common genes between Parkinson’s disease and Alzheimer’s disease identified from SPOKE include APP, APOE, MAPT, PSEN1, and SNCA, with provenance from the DISEASES database and GWAS Catalog. Additional Knowledge:
TREM2 is also a common gene between Parkinson’s disease and Alzheimer’s disease, supported by both GWAS Catalog and DISEASES database.
In conclusion, the genes APP, APOE, MAPT, PSEN1, SNCA, and TREM2 are common between Parkinson’s disease and Alzheimer’s disease. This information is derived from both the SPOKE knowledge base and additional biomedical knowledge. For any drug or medication suggestions, it is advised to seek guidance from a healthcare professional.
Query Type: Multi-disease symptom comparison
Features Demonstrated: Symptom analysis, disease comparison
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SECTION 1 - SPOKE-PRIORITIZED RESPONSE: Based on SPOKE knowledge base:
Fatigue:
Multiple sclerosis (MS) presents with fatigue (Provenance: NCBI PubMed). Lupus erythematosus, being an autoimmune disease, also commonly presents with fatigue. Memory Disorders:
MS presents with memory disorders (Provenance: NCBI PubMed). Lupus can also cause cognitive dysfunction, including memory issues. Muscle Spasticity:
MS presents with muscle spasticity (Provenance: NCBI PubMed). Lupus can cause muscle pain and weakness, which may be perceived similarly to spasticity. Vision Disorders:
MS presents with vision disorders (Provenance: NCBI PubMed). Lupus can cause vision problems due to inflammation of the optic nerve or other ocular issues. SPOKE knowledge base provides partial information. I’ll supplement with my trained biomedical knowledge:
Gait Disorders:
MS presents with gait disorders (Provenance: NCBI PubMed). Lupus can cause joint pain and muscle weakness, leading to difficulties in walking. Sleep Wake Disorders:
MS presents with sleep-wake disorders (Provenance: NCBI PubMed). Lupus patients often experience sleep disturbances due to pain and fatigue.
SECTION 2 - ANALYSIS WITHOUT SPOKE (USING KNOWLEDGE FROM LLM TRAINING):
Based on my trained biomedical knowledge, the shared symptoms between multiple sclerosis (MS) and lupus (systemic lupus erythematosus) include:
Fatigue: Both conditions commonly cause significant fatigue. Cognitive Dysfunction: Memory issues and cognitive impairment are seen in both diseases. Muscle and Joint Pain: While MS causes muscle spasticity, lupus can cause muscle pain and joint pain. Vision Problems: Both diseases can lead to vision disturbances. Gait and Mobility Issues: Both conditions can affect mobility, though through different mechanisms. Sleep Disturbances: Both conditions can lead to sleep problems due to pain, fatigue, or other symptoms.
SECTION 3 - SUMMARY:
From Section 1 (with SPOKE):
Shared symptoms between MS and lupus include fatigue, memory disorders, muscle spasticity (or muscle pain in lupus), vision disorders, gait disorders, and sleep-wake disorders. Provenance for these associations is primarily from NCBI PubMed. From Section 2 (without SPOKE):
Additional shared symptoms include cognitive dysfunction, muscle and joint pain, and mobility issues. These insights are based on general biomedical knowledge.
Summary: Both multiple sclerosis and lupus share several symptoms, including fatigue, cognitive dysfunction, muscle and joint pain, vision problems, gait and mobility issues, and sleep disturbances. The SPOKE knowledge base provides a solid foundation for these associations, supplemented by broader biomedical knowledge to fill in any gaps. For any specific treatment or medication advice, it is crucial to consult a healthcare professional.
Query Type: Disease-drug relationships
Features Demonstrated: Treatment options, drug information
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SECTION 1 - SPOKE-PRIORITIZED RESPONSE:
Based on SPOKE knowledge base:
Alprazolam: Treats generalized anxiety disorder. Provenance of this association is DrugCentral. Buspirone: Treats generalized anxiety disorder. Provenance of this association is DrugCentral. Citalopram: Treats generalized anxiety disorder. Provenance of this association is DrugCentral. Paroxetine: Treats generalized anxiety disorder. Provenance of this association is DrugCentral. To provide a complete answer, I’ll add information from my trained biomedical knowledge along with this:
Duloxetine: An SNRI (serotonin-norepinephrine reuptake inhibitor) commonly used to treat generalized anxiety disorder. Escitalopram: An SSRI (selective serotonin reuptake inhibitor) often prescribed for generalized anxiety disorder. Sertraline: Another SSRI that is frequently used to manage generalized anxiety disorder. Venlafaxine: An SNRI that is also effective in treating generalized anxiety disorder.
SECTION 2 - ANALYSIS WITHOUT SPOKE (USING KNOWLEDGE FROM LLM TRAINING)
Based on my trained biomedical knowledge:
Alprazolam: A benzodiazepine used for short-term relief of severe anxiety symptoms. Buspirone: An anxiolytic that is particularly effective for chronic anxiety and has a lower risk of dependency compared to benzodiazepines. Citalopram: An SSRI that helps in reducing anxiety symptoms by increasing serotonin levels in the brain. Paroxetine: Another SSRI that is effective in treating generalized anxiety disorder. Duloxetine: An SNRI that helps in managing anxiety by affecting both serotonin and norepinephrine levels. Escitalopram: An SSRI known for its efficacy in treating generalized anxiety disorder. Sertraline: An SSRI that is widely used for anxiety disorders. Venlafaxine: An SNRI that is effective for generalized anxiety disorder.
SECTION 3 - SUMMARY
From Section 1 (with SPOKE):
SPOKE provides information on four drugs: Alprazolam, Buspirone, Citalopram, and Paroxetine, all of which are associated with treating generalized anxiety disorder (Provenance: DrugCentral). Additional drugs from biomedical knowledge include Duloxetine, Escitalopram, Sertraline, and Venlafaxine. From Section 2 (without SPOKE):
The same four drugs (Alprazolam, Buspirone, Citalopram, and Paroxetine) are identified, along with additional drugs (Duloxetine, Escitalopram, Sertraline, and Venlafaxine) that are commonly used for generalized anxiety disorder.
In conclusion, both SPOKE and trained biomedical knowledge identify Alprazolam, Buspirone, Citalopram, and Paroxetine as treatments for generalized anxiety disorder. Additional drugs such as Duloxetine, Escitalopram, Sertraline, and Venlafaxine are also effective and commonly used. Always consult a healthcare professional for personalized medical advice and treatment options.
Query Type: Disease ontology
Features Demonstrated: Disease classification, subtypes
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SECTION 1 - SPOKE-PRIORITIZED RESPONSE: Based on SPOKE knowledge base:
Balo concentric sclerosis:
A type of multiple sclerosis characterized by concentric layers of demyelination. Provenance: Disease Ontology. Primary progressive multiple sclerosis:
A form of multiple sclerosis where the disease progresses steadily from onset without relapses. Provenance: Disease Ontology. Progressive relapsing multiple sclerosis:
A type of multiple sclerosis that shows steady progression of disability from onset but with clear acute relapses. Provenance: Disease Ontology. Relapsing-remitting multiple sclerosis:
The most common form of multiple sclerosis, characterized by clear relapses of disease activity followed by periods of remission. Provenance: Disease Ontology. Secondary progressive multiple sclerosis:
Initially presents as relapsing-remitting multiple sclerosis but later transitions to a phase of steady progression. Provenance: Disease Ontology. To provide a complete answer, I’ll add information from my trained biomedical knowledge along with this:
Clinically isolated syndrome (CIS): A first episode of neurological symptoms lasting at least 24 hours, caused by inflammation or demyelination in the central nervous system. It may or may not develop into multiple sclerosis.
SECTION 2 - ANALYSIS WITHOUT SPOKE (USING KNOWLEDGE FROM LLM TRAINING):
Based on my trained biomedical knowledge, the different types of multiple sclerosis (MS) include:
Clinically Isolated Syndrome (CIS):
A single episode of neurological symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system. It may or may not progress to MS. Relapsing-Remitting MS (RRMS):
Characterized by episodes of new or increasing neurological symptoms (relapses) followed by periods of partial or complete recovery (remissions). Primary Progressive MS (PPMS):
Marked by a steady progression of symptoms from the onset, without early relapses or remissions. Secondary Progressive MS (SPMS):
Initially begins as relapsing-remitting MS but transitions into a phase of steady progression of symptoms with or without relapses. Progressive-Relapsing MS (PRMS):
A rare form of MS that shows steady progression of disability from onset but with clear acute relapses.
SECTION 3 - SUMMARY:
From Section 1 (with SPOKE):
The SPOKE knowledge base identifies several types of multiple sclerosis, including Balo concentric sclerosis, primary progressive multiple sclerosis, progressive relapsing multiple sclerosis, relapsing-remitting multiple sclerosis, and secondary progressive multiple sclerosis. Provenance for these associations is primarily from the Disease Ontology. From Section 2 (without SPOKE):
My trained biomedical knowledge adds to the list by including Clinically Isolated Syndrome (CIS) and provides detailed descriptions of each type of MS, including relapsing-remitting MS, primary progressive MS, secondary progressive MS, and progressive-relapsing MS.
Summary:
Both sources agree on the main types of multiple sclerosis: relapsing-remitting MS, primary progressive MS, secondary progressive MS, and progressive-relapsing MS. The SPOKE knowledge base also includes Balo concentric sclerosis, while my trained biomedical knowledge adds Clinically Isolated Syndrome (CIS) to the list. For a comprehensive understanding, it is essential to consider both sources. Always consult a healthcare professional for personalized medical advice.
Note: These examples were generated using KG-RAG in Versa with GPT-4o model.