Differential Diagnosis of Hematologic and Solid Tumors Using Targeted Transcriptome and Artificial Intelligence

Am J Pathol. 2023 Jan;193(1):51-59. doi: 10.1016/j.ajpath.2022.09.006. Epub 2022 Oct 13.


Diagnosis and classification of tumors is increasingly dependent on biomarkers. RNA expression profiling using next-generation sequencing provides reliable and reproducible information on the biology of cancer. This study investigated targeted transcriptome and artificial intelligence for differential diagnosis of hematologic and solid tumors. RNA samples from hematologic neoplasms (N = 2606), solid tumors (N = 2038), normal bone marrow (N = 782), and lymph node control (N = 24) were sequenced using next-generation sequencing using a targeted 1408-gene panel. Twenty subtypes of hematologic neoplasms and 24 subtypes of solid tumors were identified. Machine learning was used for diagnosis between two classes. Geometric mean naïve Bayesian classifier was used for differential diagnosis across 45 diagnostic entities with assigned rankings. Machine learning showed high accuracy in distinguishing between two diagnoses, with area under the curve varying between 1 and 0.841. Geometric mean naïve Bayesian algorithm was trained using 3045 samples and tested on 1415 samples, and showed correct first-choice diagnosis in 100%, 88%, 85%, 82%, 88%, 72%, and 72% of acute lymphoblastic leukemia, acute myeloid leukemia, diffuse large B-cell lymphoma, colorectal cancer, lung cancer, chronic lymphocytic leukemia, and follicular lymphoma cases, respectively. The data indicate that targeted transcriptome combined with artificial intelligence are highly useful for diagnosis and classification of various cancers. Mutation profiles and clinical information can improve these algorithms and minimize errors in diagnoses.

MeSH terms

  • Artificial Intelligence
  • Bayes Theorem
  • Diagnosis, Differential
  • Hematologic Neoplasms* / diagnosis
  • Hematologic Neoplasms* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • RNA
  • Transcriptome / genetics


  • RNA