ADS Capstone Chronicles Revised

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‭drug‬ ‭interactions‬ ‭(DrugBank,‬ ‭2024),‬ ‭standardized‬ ‭drug‬ ‭information‬ ‭from‬ ‭RxNorm‬ ‭(National‬ ‭Institutes‬ ‭of‬ ‭Health‬ ‭[NIH],‬‭n.d.),‬‭and‬‭the‬‭Adverse‬‭Drug‬‭Reaction‬ ‭Classification‬ ‭System‬ ‭(ADReCS;‬ ‭Cai‬ ‭et‬‭al.,‬ ‭2015).‬‭Other‬‭research‬‭groups‬‭have‬‭compiled‬ ‭drug‬ ‭information‬ ‭from‬ ‭these‬ ‭sources‬ ‭to‬ ‭apply‬ ‭machine‬ ‭learning‬ ‭and‬ ‭reinforcement‬ ‭learning‬ ‭methods‬ ‭to‬ ‭drug‬ ‭interactions,‬ ‭side‬ ‭effects, and adverse events data.‬ ‭3.1 ADReCS‬ ‭An‬‭early‬‭tool‬‭that‬‭combined‬‭FAERS‬‭adverse‬ ‭drug‬ ‭reaction‬‭with‬‭drug‬‭interaction‬‭data‬‭and‬ ‭chemical‬ ‭structures‬ ‭is‬ ‭the‬ ‭ADReCS‬ ‭dashboard‬ ‭and‬ ‭database.‬ ‭It‬ ‭contains‬ ‭hierarchical,‬ ‭standardized‬ ‭adverse‬ ‭drug‬ ‭reaction‬ ‭terms‬ ‭and‬ ‭drug‬ ‭compounds‬ ‭(http://bioinf.xmu.edu.cn/ADReCS/;‬ ‭Cai‬ ‭et‬ ‭al.,‬ ‭2015).‬ ‭The‬ ‭system‬ ‭was‬ ‭developed‬ ‭to‬ ‭combat‬ ‭inconsistencies,‬ ‭synonyms,‬ ‭and‬ ‭abbreviations‬ ‭used‬ ‭in‬ ‭reporting.‬ ‭The‬ ‭database‬ ‭dictionary‬ ‭can‬ ‭be‬ ‭used‬ ‭to‬ ‭clean‬ ‭datasets‬ ‭from‬ ‭FAERS‬ ‭by‬ ‭linking‬ ‭terms‬ ‭to‬‭a‬ ‭standard‬ ‭spelling.‬ ‭The‬ ‭system‬ ‭also‬ ‭links‬ ‭drugs‬ ‭with‬ ‭associated‬ ‭adverse‬ ‭reactions,‬ ‭chemical‬ ‭structures,‬ ‭and‬ ‭Simplified‬ ‭Molecular‬ ‭Input‬ ‭Line‬ ‭Entry‬ ‭Specification‬ ‭(SMILES) structures (Weininger, 1988).‬ ‭3.2 Classification Models‬ ‭In‬ ‭addition‬ ‭to‬ ‭the‬ ‭existing‬ ‭databases‬ ‭and‬ ‭dashboards‬ ‭linked‬ ‭above,‬ ‭many‬ ‭researchers‬ ‭have‬ ‭utilized‬ ‭machine‬ ‭learning‬ ‭to‬ ‭predict‬ ‭drug‬ ‭side‬ ‭effects‬ ‭and‬ ‭frequencies.‬ ‭In‬ ‭2017,‬ ‭Lee‬ ‭et‬ ‭al.‬ ‭generated‬ ‭three‬ ‭classification‬ ‭models,‬ ‭Bayesian‬ ‭classifier,‬ ‭k-nearest‬ ‭neighbor,‬ ‭and‬ ‭random‬ ‭forest‬ ‭models,‬ ‭using‬ ‭10-fold‬ ‭cross‬ ‭validation‬‭to‬‭predict‬‭drug‬‭side‬ ‭effects.‬‭Data‬‭sources‬‭included‬‭DrugBank‬‭for‬ ‭biological‬ ‭aspects‬ ‭of‬ ‭drug‬ ‭data‬ ‭(Wishart‬ ‭et‬ ‭al.,‬‭2018),‬‭PubChem‬‭Compound‬‭ID‬‭for‬‭drug‬ ‭mapping‬ ‭(NCBI,‬ ‭n.d.),‬ ‭UniProt‬ ‭Consortium‬ ‭Knowledgebase‬ ‭for‬ ‭protein‬ ‭information‬ ‭(2021),‬ ‭SMILES‬ ‭for‬ ‭drug‬ ‭structure‬ ‭data‬ ‭(Weininger,‬ ‭1988),‬ ‭the‬ ‭National‬ ‭Drug‬

‭File-Reference‬ ‭Terminology‬ ‭for‬ ‭therapeutic‬ ‭indications‬ ‭of‬ ‭drugs‬ ‭(U.S.‬ ‭Department‬ ‭of‬ ‭Veterans‬ ‭Affairs,‬ ‭n.d.),‬ ‭and‬ ‭the‬ ‭Side‬ ‭Effect‬ ‭Resource‬ ‭(SIDER)‬ ‭database‬ ‭for‬ ‭side‬ ‭effect‬ ‭data‬ ‭(Kuhn‬ ‭et‬ ‭al.,‬ ‭2016).‬ ‭The‬ ‭drug‬ ‭structures,‬ ‭side‬ ‭effects,‬ ‭and‬ ‭therapeutic‬ ‭indications‬ ‭were‬ ‭represented‬ ‭as‬ ‭binary‬ ‭features‬‭in‬‭classification‬‭(present‬‭or‬‭absent).‬ ‭The‬‭initial‬‭total‬‭feature‬‭count‬‭was‬‭7257;‬‭due‬ ‭to‬ ‭the‬ ‭high‬ ‭number‬ ‭of‬ ‭features,‬ ‭they‬ ‭also‬ ‭explored‬ ‭dimensionality‬ ‭reduction‬ ‭techniques‬ ‭to‬ ‭reduce‬‭the‬‭number‬‭of‬‭features‬ ‭due‬ ‭to‬ ‭class‬ ‭imbalance.‬ ‭They‬ ‭assessed‬ ‭the‬ ‭model‬‭with‬‭three‬‭available‬‭datasets:‬‭Pauwels‬ ‭et‬‭al.’s‬‭(2011),‬ ‭Mizutani‬‭et‬‭al.’s‬‭(2012),‬‭and‬ ‭Liu’‬ ‭et‬ ‭al.’s‬ ‭(2012).‬ ‭Models‬ ‭attained‬ ‭high‬ ‭accuracy,‬ ‭but‬ ‭lacked‬ ‭performance‬ ‭in‬ ‭precision,‬ ‭recall,‬ ‭and‬ ‭F-measure.‬ ‭Overall,‬ ‭the‬ ‭random‬ ‭forest‬ ‭model‬ ‭performed‬ ‭best,‬ ‭with‬ ‭an‬ ‭accuracy‬ ‭of‬ ‭0.951,‬ ‭precision‬ ‭of‬ ‭0.710,‬‭recall‬‭of‬‭0.304,‬‭and‬‭F-score‬‭of‬‭0.426.‬ ‭In‬ ‭the‬ ‭study's‬ ‭conclusion,‬ ‭they‬ ‭mentioned‬ ‭that‬ ‭some‬ ‭drugs‬ ‭were‬‭harder‬‭to‬‭predict‬‭than‬ ‭others;‬‭despite‬‭this,‬‭the‬‭study‬‭confirmed‬‭that‬ ‭machine‬ ‭learning‬ ‭models‬ ‭have‬ ‭feasibility‬ ‭and‬ ‭effectiveness‬ ‭in‬ ‭predicting‬ ‭side‬ ‭effects.‬ ‭They‬ ‭also‬ ‭addressed‬ ‭the‬ ‭limitation‬ ‭that‬ ‭model‬ ‭interpretability‬ ‭from‬ ‭the‬ ‭perspective‬ ‭of‬ ‭physicians‬ ‭could‬ ‭be‬ ‭improved,‬ ‭specifically‬ ‭by‬ ‭adding‬ ‭statistically‬ ‭significant‬ ‭measures,‬ ‭and‬ ‭clinical‬ ‭meaningfulness.‬ ‭3.3 Recommender Methods‬ ‭Zhang‬ ‭et‬ ‭al.‬ ‭(2016)‬ ‭used‬ ‭two‬ ‭recommender‬ ‭methods,‬ ‭integrated‬ ‭neighborhood-based‬ ‭method‬ ‭and‬ ‭restricted‬ ‭Boltzmann‬ ‭machine-based‬ ‭method,‬ ‭and‬ ‭their‬ ‭combined‬ ‭ensemble,‬‭to‬‭train‬‭models‬‭on‬‭the‬‭relationship‬ ‭between‬ ‭approved‬ ‭drugs,‬ ‭side‬ ‭effects,‬ ‭and‬ ‭drug-side‬ ‭effect‬ ‭associations.‬ ‭The‬ ‭models‬ ‭were‬ ‭used‬ ‭to‬ ‭predict‬ ‭new‬ ‭side‬ ‭effects‬ ‭for‬ ‭drugs.‬‭Data‬‭was‬‭sourced‬‭from‬‭SIDER‬‭(Kuhn‬ ‭et‬ ‭al.,‬ ‭2016),‬ ‭PubChem‬ ‭(NCBI,‬ ‭n.d.),‬ ‭DrugBank‬‭(Wishart‬‭et‬‭al.,‬‭2018),‬‭and‬‭Kyoto‬ ‭Encyclopedia‬ ‭of‬ ‭Genes‬ ‭and‬ ‭Genomes‬

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