Reimann, MajaMajaReimannAvsar, KorkutKorkutAvsarDiNardo, Andrew RAndrew RDiNardoGoldmann, TorstenTorstenGoldmannGünther, GunarGunarGüntherHoelscher, MichaelMichaelHoelscherIbraim, ElmiraElmiraIbraimKalsdorf, BarbaraBarbaraKalsdorfKaufmann, Stefan H EStefan H EKaufmannKöhler, NiklasNiklasKöhlerMandalakas, Anna MAnna MMandalakasMaurer, Florian PFlorian PMaurerMüller, MariusMariusMüllerNitschkowski, DörteDörteNitschkowskiOlaru, Ioana DIoana DOlaruPopa, CristinaCristinaPopaRachow, AndreaAndreaRachowRolling, ThierryThierryRollingSalzer, Helmut J FHelmut J FSalzerSanchez-Carballo, PatriciaPatriciaSanchez-CarballoSchuhmann, MarenMarenSchuhmannSchaub, DagmarDagmarSchaubSpinu, VictorVictorSpinuTerhalle, ElenaElenaTerhalleUnnewehr, MarkusMarkusUnnewehrZielinski, Nika JNika JZielinskiHeyckendorf, JanJanHeyckendorfLange, ChristophChristophLange2025-02-252025-02-252024https://boris-portal.unibe.ch/handle/20.500.12422/205112Rationale Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.Objective Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.Methods Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.Results The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of 27 genes (TB27) for predicting the remaining time to culture conversion (TCC) at any given time. In the test dataset, predicted TCC and observed TCC achieved a correlation coefficient of r=0.98. An external validation cohort of 34 patients shows a correlation between predicted and observed days to TCC also of r=0.98.Conclusion We identified and validated a whole blood-based RNA signature (TB27) that demonstrates an excellent agreement between predicted and observed times to M. tuberculosis culture conversion during tuberculosis therapy. TB27 is a potential useful biomarker for anti-tuberculosis drug development and for prediction of treatment responses in clinical practice.enbiomarkerprecision medicinesystems biologytherapy responsetuberculosis treatment600 - Technology::610 - Medicine & healtharticle10.48620/855113991114410.20411/pai.v10i1.770