title: Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder.
abstract: OBJECTIVE
  Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor.
  
  
  METHODS
  Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction.
  
  
  RESULTS
  The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set.
  
  
  CONCLUSIONS
  Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management.
authors.affiliation: University of Southern California, Los Angeles, California; Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Anirban P
authors.initials: AP
authors.lastname: Mitra
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Sheetal A
authors.initials: SA
authors.lastname: Mitra
authors.affiliation: Everist Genomics, Ann Arbor, Michigan.
authors.forename: Arpit A
authors.initials: AA
authors.lastname: Almal
authors.affiliation: University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Steven
authors.affiliation: University of Southern California, Los Angeles, California.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Skinner
authors.affiliation: Everist Genomics, Ann Arbor, Michigan.
authors.forename: David W
authors.initials: DW
authors.lastname: Fry
authors.affiliation: Everist Genomics, Ann Arbor, Michigan.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Lenehan
authors.affiliation: Everist Genomics, Ann Arbor, Michigan.
authors.forename: William P
authors.initials: WP
authors.lastname: Worzel
authors.affiliation: University of Miami, Miami, Florida. Electronic address: RCote@med.miami.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cote
mesh_terms: D000368:Aged; D000465:Algorithms; D001185:Artificial Intelligence; D001706:Biopsy; D002295:Carcinoma, Transitional Cell / Q000473:pathology* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000069550:Machine Learning; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000601:surgery
keywords: algorithms; genome; local; neoplasm recurrence; software; urinary bladder neoplasms