biostudies-literatureUnknown11(5)Yu ZDirect data-independent acquisition (DIA) in liquid chromatography-tandem mass spectrometry (LC-MS/MS) has developed into a powerful methodology for proteomics. Herein, we directly compare the performance of two widely used DIA computational platformsSpectronaut and DIA-NNusing paired tumor and peritumor tissue biopsies from human lung carcinoma (LUAD) patients, samples that one would encounter in a clinical research lab in a hospital setting. The evaluations include the following: (1) protein identification depth, (2) quantitative consistency, and (3) differential expression on the same set of LC-MS/MS runs, using nominally identical computational parameters and settings. Both Spectronaut and DIA-NN identified ∼>7600 proteins in the LUAD samples, with 7180 proteins common to both platfoACS omega8080-8093https://www.ebi.ac.uk/biostudies/studies/S-EPMC12903166biostudies-literatureSpectronaut and DIA-NN: A Comparison of their Performance in the Analysis of Lung Adenocarcinoma Biopsies.PMC12903166Zhang WChu IKDu ALi YSiu KWMZhang YMa XYu ZXu XfalseSpectronaut and DIA-NN: A Comparison of their Performance in the Analysis of Lung Adenocarcinoma Biopsies.Direct data-independent acquisition (DIA) in liquid chromatography-tandem mass spectrometry (LC-MS/MS) has developed into a powerful methodology for proteomics. Herein, we directly compare the performance of two widely used DIA computational platformsSpectronaut and DIA-NNusing paired tumor and peritumor tissue biopsies from human lung carcinoma (LUAD) patients, samples that one would encounter in a clinical research lab in a hospital setting. The evaluations include the following: (1) protein identification depth, (2) quantitative consistency, and (3) differential expression on the same set of LC-MS/MS runs, using nominally identical computational parameters and settings. Both Spectronaut and DIA-NN identified ∼>7600 proteins in the LUAD samples, with 7180 proteins common to both platfo2026-01-01T00:00:00Z2026 Feb2026-07-15T16:40:56.674Z2026-07-07T03:08:22.861ZS-EPMC129031664169623310.1021/acsomega.5c10421