Benevolent Platform Precision Medicine

ALS: Hypothesis Generation with a focus on key mechanisms and Precision Medicine based approaches 1. Targets associated with key mechanisms in neurodegeneration identified using knowledge graph based relational inference models using a “Fleet” of algorithmic models о Key mechanisms: Autophagy, mitochondrial health, proteosome function, and lysosomal function Unstructured data Target Triage TARGET ALS Hypotheses prioritised based on relevance to ALS, neurodegeneration mechanisms, druggability 1 2 3 4 00000 2. Omics/Precision medicine based approach using Target ALS collaboration dataset 612 RNA-Seq samples from 149 individuals identify subgroups of ALS patients (endotypes) with distinct molecular disease mechanisms/targets 830 10 0.00 904 02 0.00 Reported day of symptom onset minus predicted day at which ALSFRS total score should be 48 post symptom onset normal Target Safety Drugs? Metadata Score Tgt1 Safe Partial OPC, GCNN 0.71 120 Structured data Tgt2 Unsafe No Graph Inference SQT 0.65 100 Tgt3 Safe Yes OPC, CROM 0.51 Tgt4 Phase II Offtgts OPC 0.49 Benevolent 46 Al

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