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Background  How to treat a disease remains to be the most common type of clinical question. Obtaining evidence-based answers from biomedical literature is difficult. Analogical reasoning with embeddings from deep learning (embedding analogies) may extract such biomedical facts, although the state-of-the-art focuses on pair-based proportional (pairwise) analogies such as man:woman::king:queen (“ queen = −man +king +woman ”).    Objective  This study aimed to systematically extract disease treatment statements with a Semantic Deep Learning (SemDeep) approach underpinned by prior knowledge and another type of 4-term analogy (other than pairwise).    Methods  As preliminaries, we investigated Continuous Bag-of-Words (CBOW) embedding analogies in a common-English corpus with five lines of text and observed a type of 4-term analogy (not pairwise) applying the 3CosAdd formula and relating the semantic fields  person  and  death : “dagger = −Romeo +die +died” (search query: − Romeo +die +died ). Our SemDeep approach worked with pre-existing items of knowledge (what is known) to make inferences sanctioned by a 4-term analogy (search query − x +z1 +z2 ) from CBOW and Skip-gram embeddings created with a PubMed systematic reviews subset (PMSB dataset). Stage1: Knowledge acquisition. Obtaining a set of terms, candidate y, from embeddings using vector arithmetic. Some n-gram pairs from the cosine and validated with evidence (prior knowledge) are the input for the 3cosAdd, seeking a type of 4-term analogy relating the semantic fields disease and treatment. Stage 2: Knowledge organization. Identification of candidates sanctioned by the analogy belonging to the semantic field treatment and mapping these candidates to unified medical language system Metathesaurus concepts with MetaMap. A concept pair is a brief disease treatment statement (biomedical fact). Stage 3: Knowledge validation. An evidence-based evaluation followed by human validation of biomedical facts potentially useful for clinicians.    Results  We obtained 5352 n-gram pairs from 446 search queries by applying the 3CosAdd. The microaveraging performance of MetaMap for candidate  y  belonging to the semantic field  treatment  was F-measure=80.00% (precision=77.00%, recall=83.25%). We developed an empirical heuristic with some predictive power for  clinical winners , that is, search queries bringing candidate  y  with evidence of a therapeutic intent for target disease  x . The search queries  -asthma +inhaled_corticosteroids +inhaled_corticosteroid  and  -epilepsy +valproate +antiepileptic_drug  were  clinical winners , finding eight evidence-based beneficial treatments.    Conclusions  Extracting treatments with therapeutic intent by analogical reasoning from embeddings (423K n-grams from the PMSB dataset) is an ambitious goal. Our SemDeep approach is knowledge-based, underpinned by embedding analogies that exploit prior knowledge. Biomedical facts from embedding analogies (4-term type, not pairwise) are potentially useful for clinicians. The heuristic offers a practical way to discover beneficial treatments for well-known diseases. Learning from deep learning models does not require a massive amount of data. Embedding analogies are not limited to pairwise analogies; hence, analogical reasoning with embeddings is underexploited.

Semantic Deep Learning: Prior Knowledge and a Type of Four-Term Embedding Analogy to Acquire Treatments for Well-Known Diseases