MetaboLights

application/xml

ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/m_MTBLS140_NEG_nephron_toxicity_mass_spectrometry_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/m_MTBLS140_POS_nephron_toxicity_mass_spectrometry_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/a_MTBLS140_LC-MS_POS_nephron_toxicity_mass_spectrometry.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/s_MTBLS140.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/a_MTBLS140_LC-MS_NEG_nephron_toxicity_mass_spectrometry-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/037_CRa_H9M5_M470_Blank_09_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/007_CRa_H9M5_M470_L01_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/012_CRa_H9M5_M470_C01_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/039_CRa_H9M5_M470_C03_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/016_CRa_H9M5_M470_H01_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/008_CRa_H9M5_M470_H14_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/016_CRa_H9M5_M470_H01_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/026_CRa_H9M5_M470_H03_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/037_CRa_H9M5_M470_Blank_09_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/012_CRa_H9M5_M470_C01_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/022_CRa_H9M5_M470_Blank_06_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/021_CRa_H9M5_M470_L03_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/013_CRa_H9M5_M470_Blank_04_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/001_CRa_H9M5_M470_Blank_01_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/008_CRa_H9M5_M470_H14_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/026_CRa_H9M5_M470_H03_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/039_CRa_H9M5_M470_C03_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/007_CRa_H9M5_M470_L01_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/020_CRa_H9M5_M470_C14_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/026_CRa_H9M5_M470_H03_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/006_CRa_H9M5_M470_H01_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/001_CRa_H9M5_M470_Blank_01_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/026_CRa_H9M5_M470_H03_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/010_CRa_H9M5_M470_L03_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/044_CRa_H9M5_M470_L14_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/027_CRa_H9M5_M470_H14_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/045_CRa_H9M5_M470_L14_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/006_CRa_H9M5_M470_H01_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/027_CRa_H9M5_M470_H14_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/045_CRa_H9M5_M470_L14_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/003_CRa_H9M5_M470_Pool_02_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/015_CRa_H9M5_M470_H14_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/022_CRa_H9M5_M470_Blank_06_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/003_CRa_H9M5_M470_Pool_02_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/036_CRa_H9M5_M470_C03_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/015_CRa_H9M5_M470_H14_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/044_CRa_H9M5_M470_L14_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/025_CRa_H9M5_M470_C03_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/036_CRa_H9M5_M470_C03_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/040_CRa_H9M5_M470_L03_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/042_CRa_H9M5_M470_Pool_06_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/042_CRa_H9M5_M470_Pool_06_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/030_CRa_H9M5_M470_C14_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/041_CRa_H9M5_M470_Blank_10_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/025_CRa_H9M5_M470_C03_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/028_CRa_H9M5_M470_Blank_07_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/006_CRa_H9M5_M470_H01_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/037_CRa_H9M5_M470_Blank_09_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/008_CRa_H9M5_M470_H14_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/018_CRa_H9M5_M470_Blank_05_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/032_CRa_H9M5_M470_Blank_08_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/036_CRa_H9M5_M470_C03_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/041_CRa_H9M5_M470_Blank_10_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/019_CRa_H9M5_M470_C01_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/023_CRa_H9M5_M470_Pool_04_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/034_CRa_H9M5_M470_L01_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/033_CRa_H9M5_M470_Pool_05_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/025_CRa_H9M5_M470_C03_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/046_CRa_H9M5_M470_H03_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/028_CRa_H9M5_M470_Blank_07_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/031_CRa_H9M5_M470_H01_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/009_CRa_H9M5_M470_Blank_03_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/014_CRa_H9M5_M470_Pool_03_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/007_CRa_H9M5_M470_L01_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/010_CRa_H9M5_M470_L03_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/010_CRa_H9M5_M470_L03_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/027_CRa_H9M5_M470_H14_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/002_CRa_H9M5_M470_Pool_01_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/012_CRa_H9M5_M470_C01_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/033_CRa_H9M5_M470_Pool_05_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/011_CRa_H9M5_M470_C14_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/002_CRa_H9M5_M470_Pool_01_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/045_CRa_H9M5_M470_L14_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/018_CRa_H9M5_M470_Blank_05_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/013_CRa_H9M5_M470_Blank_04_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/005_CRa_H9M5_M470_Blank_02_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/047_CRa_H9M5_M470_Blank_11_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/021_CRa_H9M5_M470_L03_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/005_CRa_H9M5_M470_Blank_02_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/035_CRa_H9M5_M470_C01_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/022_CRa_H9M5_M470_Blank_06_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/017_CRa_H9M5_M470_H03_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/014_CRa_H9M5_M470_Pool_03_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/047_CRa_H9M5_M470_Blank_11_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/029_CRa_H9M5_M470_L01_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/031_CRa_H9M5_M470_H01_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/023_CRa_H9M5_M470_Pool_04_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/030_CRa_H9M5_M470_C14_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/044_CRa_H9M5_M470_L14_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/034_CRa_H9M5_M470_L01_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/003_CRa_H9M5_M470_Pool_02_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/046_CRa_H9M5_M470_H03_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/016_CRa_H9M5_M470_H01_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/020_CRa_H9M5_M470_C14_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/034_CRa_H9M5_M470_L01_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/005_CRa_H9M5_M470_Blank_02_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/016_CRa_H9M5_M470_H01_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/035_CRa_H9M5_M470_C01_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/035_CRa_H9M5_M470_C01_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/009_CRa_H9M5_M470_Blank_03_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/042_CRa_H9M5_M470_Pool_06_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/033_CRa_H9M5_M470_Pool_05_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/042_CRa_H9M5_M470_Pool_06_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/040_CRa_H9M5_M470_L03_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/017_CRa_H9M5_M470_H03_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/027_CRa_H9M5_M470_H14_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/017_CRa_H9M5_M470_H03_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/011_CRa_H9M5_M470_C14_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/040_CRa_H9M5_M470_L03_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/011_CRa_H9M5_M470_C14_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/029_CRa_H9M5_M470_L01_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/007_CRa_H9M5_M470_L01_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/021_CRa_H9M5_M470_L03_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/015_CRa_H9M5_M470_H14_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/015_CRa_H9M5_M470_H14_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/032_CRa_H9M5_M470_Blank_08_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/021_CRa_H9M5_M470_L03_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/014_CRa_H9M5_M470_Pool_03_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/046_CRa_H9M5_M470_H03_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/038_CRa_H9M5_M470_L14_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/001_CRa_H9M5_M470_Blank_01_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/001_CRa_H9M5_M470_Blank_01_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/038_CRa_H9M5_M470_L14_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/041_CRa_H9M5_M470_Blank_10_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/003_CRa_H9M5_M470_Pool_02_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/038_CRa_H9M5_M470_L14_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/046_CRa_H9M5_M470_H03_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/030_CRa_H9M5_M470_C14_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/020_CRa_H9M5_M470_C14_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/032_CRa_H9M5_M470_Blank_08_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/019_CRa_H9M5_M470_C01_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/029_CRa_H9M5_M470_L01_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/039_CRa_H9M5_M470_C03_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/044_CRa_H9M5_M470_L14_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/019_CRa_H9M5_M470_C01_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/014_CRa_H9M5_M470_Pool_03_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/032_CRa_H9M5_M470_Blank_08_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/039_CRa_H9M5_M470_C03_K2_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/018_CRa_H9M5_M470_Blank_05_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/040_CRa_H9M5_M470_L03_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/038_CRa_H9M5_M470_L14_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/025_CRa_H9M5_M470_C03_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/030_CRa_H9M5_M470_C14_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/023_CRa_H9M5_M470_Pool_04_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/006_CRa_H9M5_M470_H01_K1_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/009_CRa_H9M5_M470_Blank_03_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/034_CRa_H9M5_M470_L01_K1_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/036_CRa_H9M5_M470_C03_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/010_CRa_H9M5_M470_L03_K3_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/037_CRa_H9M5_M470_Blank_09_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/028_CRa_H9M5_M470_Blank_07_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/041_CRa_H9M5_M470_Blank_10_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/033_CRa_H9M5_M470_Pool_05_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/028_CRa_H9M5_M470_Blank_07_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/031_CRa_H9M5_M470_H01_K3_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/002_CRa_H9M5_M470_Pool_01_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/045_CRa_H9M5_M470_L14_K2_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/020_CRa_H9M5_M470_C14_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/009_CRa_H9M5_M470_Blank_03_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/011_CRa_H9M5_M470_C14_K2_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/002_CRa_H9M5_M470_Pool_01_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/035_CRa_H9M5_M470_C01_K2_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/012_CRa_H9M5_M470_C01_K1_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/018_CRa_H9M5_M470_Blank_05_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/013_CRa_H9M5_M470_Blank_04_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/019_CRa_H9M5_M470_C01_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/013_CRa_H9M5_M470_Blank_04_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/029_CRa_H9M5_M470_L01_K3_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/047_CRa_H9M5_M470_Blank_11_high_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/008_CRa_H9M5_M470_H14_K1_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/047_CRa_H9M5_M470_Blank_11_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/005_CRa_H9M5_M470_Blank_02_high_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/022_CRa_H9M5_M470_Blank_06_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/031_CRa_H9M5_M470_H01_K3_low_neg.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/023_CRa_H9M5_M470_Pool_04_low_pos.mzMLftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140/FILES/017_CRa_H9M5_M470_H03_K1_high_pos.mzMLprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS140Identification is based on matching the accurate masses against the theoretical mass of databases like HMDB or METLIN. Putative identifications were confirmed with tandem mass spectrometry (MS2) and retention time matching using a reference standard.MetaboLightsPublicExactive (Thermo Scientific)RP-HPLC-separations were performed at an Accela II HPLC system (Thermo Fisher Scientific, Bremen, Germany) with a 100 x 2.1 mm i.d. Hypersil Gold aQ column (Thermo Fisher Scientific) packed with 1.9 µm particles. Water (A) and acetonitrile (B) each containing 0.10 % (v/v) formic acid were used as eluents. The flow rate was 0.30 ml/min, and gradient elution was carried out as follows: 100% A for 1.5 minutes followed by a linear gradient to 100% B in 6.5 min and holding for 2 min. In the end a re-equilibration step was performed for 3.0 min at 0.0% B. The total run time was 13 minutes. The column temperature was maintained at 30 °C and 2.7 µl of sample was injected per run.Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-Based Experimental and Computational Pipeline. 10.1074/jbc.m115.644146. PMID:26055719Marc RurikUniversity of Tuebingenrenal proximal tubulepure substancemass spectrometryThe cell culture medium was removed and the cells were washed twice with ice cold PBS (Sigma-Aldrich), followed by an additional very rapid washing step with ammonium bicarbonate (185 mM, 289 mOsm, pH 7.8; Sigma-Aldrich). To preserve metabolites, 750 µl ice cold methanol containing deutero-alanine (50 µM) as internal standard were added. Two wells were pooled in an Eppendorf tube, vortexed and sonicated with an in-probe-sonicator from Branson Ultrasonics Corporation (Danbury, CT, USA) for 20 s to fully homogenize the sample. Finally, the cell lysates were centrifuged at 4 °C at 14000 rpm for 10 min. The supernatant was used for MTX and was stored at -80 °C until analysis.reference compoundHomo sapienshttps://www.ebi.ac.uk/metabolights/MTBLS140Oliver Kohlbacher. oliver.kohlbacher@uni-tuebingen.de.Paul Jennings. paul.jennings@i-med.ac.at.Christina Ranninger. christina.ranninger@sbg.ac.at.Marc Rurik. rurik@informatik.uni-tuebingen.de.Christian Huber. c.huber@sbg.ac.at.Alice Limonciel. alice.limonciel@i-med.ac.at.The raw data was converted to mzML using msconvert. Centroiding, metabolic feature detection and linking were performed using OpenMS. A feature consists of all peaks that belong to the same metabolite with a certain charge state and adduct. Features were identified separately for each sample; matching features are then linked across all samples. Feature intensities were normalized by a pairwise comparison between each sample and the sample with the most features. For each pairwise comparison we computed the average intensity ratio and multiplied all feature intensities in the respective map by the inverse.Time pointReplicateDoserurik@informatik.uni-tuebingen.deThe human renal proximal tubule cell line RPTEC/TERT1 was obtained from Evercyte GmbH (Vienna, Austria). The RPTEC/TERT1 cells [1] were cultured on 1 µm PET 24 mm tissue culture inserts for MTX and PTX, and on 0.2 µm aluminium oxide 25 mm inserts for TCX, and differentiated as previously described [2]. Briefly, cells were grown in a serum-free hormonally-defined medium for epithelial monolayer maturation and CAA exposure. After reaching a stable average trans-epithelial electrical resistance (TEER) of ~ 150 Ohm.cm^2, mature monolayers were exposed to either a high (35 µmol/l) or low (10 µmol/l) concentration of CAA or control medium, on both the apical and the basolateral sides [3]. Ref: [1] Wieser, M., et al. (2008). hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics. Am. J. Physiol. Renal Physiol. 295, F1365-F1375. [2] Wilmes, A., et al. (2013). Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress. J. Proteomics 79, 180-194. [3] Aschauer, L., et al. (2014). Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study. Toxicology in Vitro.MetabolomicsToxicitychloroacetaldehydehigh-performance liquid chromatography-mass spectrometryuntargeted metabolitescell lineToxicitychloroacetaldehydehigh-performance liquid chromatography-mass spectrometryuntargeted metabolitescell lineAn Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific) equipped with a heated-electrospray ion source operating in the positive or negative ion mode. An ESI heater temperature of 350 °C was chosen and sheath gas and aux gas flow rates were set to 20 and 5.0 arbitrary units in positive mode and to 35 and 10 in the negative mode, respectively. A sprayer voltage of 3.0 kV was applied and the resolution was set to 50,000. The mass range was split into a low mass range m/z 50-200 and a high mass range m/z 200-1000 and measured in two separate runs. The MS parameters were tuned for each method and polarity separately with selected metabolites. For the low mass range the best intensities were achieved with a capillary voltage of 25 V, tube lens voltage of 70 V, skimmer voltage of 14 V for positive and negative mode with changed polarity. The high mass range measurements were conducted with a capillary voltage of 55 V and -45 V, tube lens voltage of 115 V and -105 V, skimmer voltage of 22 V and -24 V for positive and negative mode respectively. The MS2 analysis was performed with a Q Exactive Orbitrap mass spectrometer (Thermo Fisher Scientific). For fragmentation experiments an S-lens RF level of 50, a sprayer voltage of 3.5 kV and capillary and heater temperature of 350 °C were chosen. A sheath gas flow of 50 and aux gas of 15 for positive ESI-mode and 40 and 10 for negative mode, respectively, were employed. In SIM mode (m/z 100-1000) the resolution was set to 70,000, for the data dependent fragmentation a resolution of 17,500 was chosen. In both cases the AGC target was 1 x 10^6 and the maximum injection time was set to 25 ms. The quadrupole isolation window was 1 m/z and a normalized collision energy (NCE) of 25 arbitrary units was used. The data depended fragmentation settings were an underfill ratio of 0.1% resulting in an intensity threshold for fragmentation of 4 x 10^4, the apex trigger was set from 2-5 s and molecules charged higher than 3 were excluded.L-Glutamic acidCDP-EthanolamineL-GlutamineGuanosine monophosphateAMPL-AlanineO-PhosphoethanolamineADPCytidineUntargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data. Automated data analysis workflows based on open source software (OpenMS, KNIME) enabled a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. Time- and concentration-dependent responses were clearly evident in the metabolomic profiles. To obtain a more comprehensive picture of the mode of action, transcriptomics and proteomics data were also integrated. For toxicity profiling of chloroacetaldehyde, 428 and 317 metabolite features were detectable in positive and negative modes, respectively, after stringent removal of chemical noise and unstable signals. Changes upon treatment were explored using principal component analysis, and statistically significant differences were identified using linear models for microarray assays. The analysis revealed toxic effects only for the treatment with 35 μmol·liter(-1) for 3 and 14 days. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, among other things, an activation of the Nrf2 and ATF4 pathways.Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline.Ranninger Christina C, Rurik Marc M, Limonciel Alice A, Ruzek Silke S, Reischl Roland R, Wilmes Anja A, Jennings Paul P, Hewitt Philip P, Dekant Wolfgang W, Kohlbacher Oliver O, Huber Christian G CGMass Spectrum Analysis, Mass Spectrum, methods, nephroneum, Metabolic, determination, Analyses, experimental, Metabolomes, experimental section, Profile, Liquid Chromatography, Spectrometry, Profiles, Spectrum Analyses, Spectrum Analysis, Spectroscopy, MS, tubulus renalis, chemical analysis, margin of safety, Mass, toxic potential, assay, Analysis, Nephron, experimental procedures., Metabolic Profile, Mass Spectrum Analyses, Mass Spectroscopy, mature nephron, Metabolic ProfilesDNA Oxidative, determination, Metabonomic, Nitrative Stress, Metabonomics, Principal Component Analyses, Damage, l(3)j5E7, Long Term, dmTAF[[II]]230, Donor Artificial Insemination, Tier, tubulate, primary metabolites, Oxidative DNA, Oxidative, Dmel_CG13826, CDA2, responsivity, Nitro-Oxidative Stress, High Performance Liquid Chromatography, gamma-L-Glutamyl-L-cysteinyl-glycine, symptoms, NFT2, Software Engineering, Nitro-Oxidative Stresses, Analysis, Work Flow, Oxidative Injury, Effect, DNA Damage, Computer Program, Donor Artificial, Animalia, treatment, Log-Linear Models, Oxidative Injuries, me75, Man (Taxonomy), TFIID TAF250, Analyses, cel, Glycine, Reduced, Open, 5-L-Glutamyl-L-cysteinylglycine, Oxidative Cleavage, Computer Programs and Programming, RCH04A07, Oxidative DNA Damages, D17Mit170, T1, Anti-oxidative, HPLC, Glutathione, genetic, Reduced glutathione, Oxidative Stress Injuries, Oxidative Stresses, High-Performance, Chromatography, disease management, Therapies, High-Performance Liquid, s, High Speed Liquid, Dmel_CG17894, Long-Term Effects, Therapy, screening, dTAF[[II]]230, Noise, animalia, Modern, familial, Liquid Chromatography, Longterm Effect, TAF200, Pollution, Linear Model, gamma-L-Glu-L-Cys-Gly, TAFII-250, Tl3, TAF250/230, Tl2, Source Softwares, l(3)03921, Software Tools, Programs, NRF2A, Program, Computer Applications, Workflows, TAFII250, Oxidative and Nitrosative Stress, Computer Applications Software, margin of safety, Computer Applications Softwares, Heterologous Insemination, DNA Oxidative Damages, Softwares, activation, 2-chloroacetaldehyde, Software Applications, whole organism, Source Software, signs, CG17603, TAF[[II]], kidney injury, kidney toxicity, Treatments, human, GSH, Nitro-Oxidative, Artificial Insemination, data analysis, Applications, Principal Component, Taf250, SR3-5, metabolites, Koerper, tube like, Linear, Liquid, Oxidative Stress Injury, Noise Pollution, Linear Regression, DNA, Work Flows, TAF230, Oxidative Damage, Computer Software Applications, CG13826, Oxidative Stress, d230, human being, anon-WO0153538.7, anon-WO0153538.6, Effects, Peptidomics, Antioxidative, secondary metabolites, Antioxidative Stress, dTAFII250, gamma-L-Glutamyl-L-Cysteinylglycine, Computer, EfW1, AID, Aid, Human, Stresses, N-(N-L-gamma-glutamyl-L-cysteinyl)-, DmelCG43286., Oxidative Nitrative, Homo sapiens, dmTAF1, Stress Injury, E4TF1-60, Taf230, CG4566, Oxidative Cleavages, Low, Animal, Metabolomic, Log-Linear, CNC, Cnc, Models, Man, Oxidative Damages, aid, Application, TAF250, Insemination, study, Open Source Softwares, reactivity, Taf200, Injury, dTAF[[II]]250, Longterm, cell, Software Application, Open Source Software, NRF2, Taf1p, N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine, Nrf2, metazoa, Long-Term, High-Performance Liquid Chromatographies, Computer Software Application, gamma L Glutamyl L Cysteinylglycine, renal toxicity, dTAF250, data processing, Tools, Anti oxidative Stress, Oxidative DNA Damage, Antioxidative Stresses, HEL-S-284, high concentration, gamma L Glu L Cys Gly, Ultra Performance Liquid Chromatography, Chronic, HIGM2, toxic potential, Long-Term Effect, UPLC, TAF, Model, Heterologous, High-Performance Liquid Chromatography, Applications Software, Open Source, TAF[[II]]250, findings, cou, Computer Software, body, TSH1, Regressions, Log Linear Models, l(3)84Ab, whole body, BG:DS00004.13, Anti-oxidative Stresses, NY-CO-33, tube-shaped, Cell, Tool, Human Donor, dTAF230, CAA, Oxidative Nitrative Stress, BcDNA:RE05559, Software Tool, Linear Regressions, Lr, p230, Oxidative Nitrative Stresses, Metazoa, Long Term Effects, chemical analysis, TAF[[II]]250/230, TFIID, CG43286, Donor, Software, Reduced Glutathione, SDCCAG33, CG17894, Artificial, Taf[[II]]250, Log-Linear Model, TAF[[II]]230, Anti-oxidative Stress, DNA Oxidative Damage, chloroacetaldehyde hydrate, Arp2, ARP2, Engineering, metabolite, CG4578, cerebral amyloid angiopathy, CNC_DROME, TAF[II]250, Cleavage, Longterm Effects, Noises, Computer Programs, AI194320, High Pressure, 5134, DmelCG17603, Applications Softwares, Regression, Therapeutic, Data, Modern Man, Stress, Bra, Treatment, E4TF1A, High Performance Liquid, Glutathione-SH, assay, response, Nitro Oxidative Stress, Data Analyses, TAF1DNA Oxidative, Product, determination, Metabonomic, Nitrative Stress, Metabonomics, Tumor, Principal Component Analyses, Damage, l(3)j5E7, Long Term, Donor Artificial Insemination, Tier, tubulate, primary metabolites, Oxidative DNA, Oxidative, Dmel_CG13826, CDA2, responsivity, Pharmaceutical Product, Nitro-Oxidative Stress, High Performance Liquid Chromatography, gamma-L-Glutamyl-L-cysteinyl-glycine, symptoms, NFT2, 3, Software Engineering, Nitro-Oxidative Stresses, Analysis, Work Flow, Oxidative Injury, Effect, DNA Damage, Computer Program, Donor Artificial, Animalia, Mass Spectrum Analysis, 929, treatment, DmelCG8669, Log-Linear Models, umol, Oxidative Injuries, Iso-Endoxan, Man (Taxonomy), Analyses, Glycine, long, N, Reduced, Open, Asta Z 4942, 5-L-Glutamyl-L-cysteinylglycine, Oxidative Cleavage, Computer Programs and Programming, RCH04A07, Oxidative DNA Damages, Anti-oxidative, HPLC, Glutathione, Reduced glutathione, NSC 109724, NSC109724, Oxidative Stress Injuries, µmol, Oxidative Stresses, High-Performance, malignant neoplasm, medicine, Pharmaceutical, l, 2H-1, Chromatography, disease management, Therapies, High-Performance Liquid, Malignancies, High Speed Liquid, Dmel_CG17894, Long-Term Effects, Tumors, NSC 109, Therapy, screening, Noise, animalia, Modern, Atf-4, Liquid Chromatography, Longterm Effect, Pollution, Linear Model, gamma-L-Glu-L-Cys-Gly, Spectrum Analysis, Source Softwares, l(3)03921, Software Tools, Programs, NRF2A, Spectroscopy, Program, Computer Applications, Workflows, Benign, Oxidative and Nitrosative Stress, Computer Applications Software, margin of safety, Computer Applications Softwares, Heterologous Insemination, Pharmaceutic, DNA Oxidative Damages, Softwares, l(2)crc, 724, activation, DmelCG43286, 2-chloroacetaldehyde, Software Applications, whole organism, Source Software, Spectrometry, 2-oxide, signs, C|ATF, Benign Neoplasms, Treatments, human, GSH, Malignant Neoplasms, Nitro-Oxidative, ATF-4, Artificial Insemination, data analysis, Applications, Principal Component, metabolites, Koerper, tube like, Linear, Liquid, microarray, CG8669, Oxidative Stress Injury, Noise Pollution, Linear Regression, DNA, ATF4/crc, Work Flows, Oxidative Damage, Computer Software Applications, CG13826, Oxidative Stress, human being, anon-WO0153538.7, anon-WO0153538.6, CREB-2, Effects, Peptidomics, Antioxidative, Neoplasms, Benign Neoplasm, secondary metabolites, Antioxidative Stress, gamma-L-Glutamyl-L-Cysteinylglycine, Spectrum Analyses, Computer, Malignant, AID, Aid, Human, Stresses, N-(N-L-gamma-glutamyl-L-cysteinyl)-, Oxidative Nitrative, Homo sapiens, Iso Endoxan, dATF-4, Stress Injury, E4TF1-60, Holoxan, Mass, CG4566, Oxidative Cleavages, Animal, Metabolomic, Log-Linear, CNC, Cnc, Models, Man, Oxidative Damages, aid, Mass Spectroscopy, Application, Drugs, Insemination, study, Open Source Softwares, reactivity, NSC-109, Injury, Malignancy, Longterm, Software Application, Open Source Software, NRF2, N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine, Nrf2, metazoa, Ire1, Long-Term, NSC-109724, Outlines, High-Performance Liquid Chromatographies, Computer Software Application, gamma L Glutamyl L Cysteinylglycine, Neoplasias, drugs, data processing, 3-bis(2-chloroethyl)tetrahydro-, Tools, Anti oxidative Stress, Oxidative DNA Damage, Antioxidative Stresses, HEL-S-284, gamma L Glu L Cys Gly, Ultra Performance Liquid Chromatography, HIGM2, toxic potential, Long-Term Effect, UPLC, Preparation, Model, Heterologous, Cancer, Pharmaceuticals, High-Performance Liquid Chromatography, Applications Software, Products, Open Source, findings, Malignant Neoplasm, Computer Software, body, drug, Regressions, Log Linear Models, whole body, Anti-oxidative Stresses, tube-shaped, Cell, Tool, Human Donor, TXREB, Oxidative Nitrative Stress, BcDNA:RE05559, Software Tool, Linear Regressions, MS, MT, Oxidative Nitrative Stresses, Metazoa, chemical analysis, Long Term Effects, Neoplasm, CREB2, Isophosphamide, CG43286, Donor, Software, Reduced Glutathione, Mass Spectrum Analyses, CG17894, Artificial, Mass Spectrum, primary cancer, Log-Linear Model, Anti-oxidative Stress, Pharmaceutic Preparations, DNA Oxidative Damage, chloroacetaldehyde hydrate, Arp2, ARP2, Engineering, metabolite, CG4578, CNC_DROME, NSC109, Cancers, Cleavage, Iphosphamide, malignant tumor, Longterm Effects, Noises, Drug, Computer Programs, AI194320, TAXREB67, Preparations, High Pressure, 5134, Applications Softwares, Atf4., Regression, 2-Oxazaphosphorin-2-amine, Therapeutic, Data, concentration, Modern Man, Stress, Treatment, E4TF1A, High Performance Liquid, Glutathione-SH, Isofosfamide, assay, response, Pharmaceutical Products, Nitro Oxidative Stress, Neoplasia, Data Analyses, Pharmaceutical PreparationWAP3, methods, nephroneum, Metabolic, determination, experimental, Metabolomes, experimental section, Profile, Liquid Chromatography, Profiles, ESI, High-Performance Liquid Chromatographies, HPLC, WFDC14, experimental procedures, High Pressure, High-Performance, tubulus renalis, chemical analysis, Chromatography, High Performance Liquid Chromatography, margin of safety, Ultra Performance Liquid Chromatography, Liquid, High-Performance Liquid, Chronic, High Speed Liquid, High Performance Liquid, toxic potential., assay, UPLC, Nephron, Metabolic Profile, mature nephron, Metabolic Profiles, High-Performance Liquid ChromatographyfalseMetabolome analysis via an HPLC-ESI-MS-based experimental and computational pipeline for chronic nephron toxicity profilingUntargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the reduction of expensive and laborious animal models. Here we describe a chronic nephrotoxicity study conducted on a human renal proximal tubular epithelial cell line (RPTEC/TERT1) treated with low (10 µM) and high (35 µM) concentrations of chloroacetaldehyde (CAA) – a known nephrotoxic compound. The presented toxicity study followed two major strategies; the first was to establish an automated and easy to use untargeted metabolomics workflow for HPLC-MS data and second to find time- and dose dependent toxicant-induced cell responses at the metabolite level. The metabolomic changes were integrated with transcriptomics and proteomics data to obtain a more comprehensive picture of the mode of action. Automated data analysis workflows based on open-source software (OpenMS and KNIME) enable a comprehensive and reproducible analysis of the complex and voluminous metabolomics data produced by the profiling approach. For toxicity profiling of CAA, 428 and 317 metabolite features were detectable in positive and negative mode, respectively, after removal of chemical noise and unstable signals. Changes upon treatment were visually explored using principal component analysis and statistically significant differences identified using linear models (LIMMA). The analysis revealed toxic effects only for the high concentration treatment for day 3 and day 14. The most regulated metabolites were glutathione and metabolites related to the oxidative stress response of the cells. These findings are corroborated by proteomics and transcriptomics data, which show, amongst others, an activation of the Nrf2 pathway.2015-09-072014-11-06MTBLS140MTBLC16010MTBLC15603MTBLC17191MTBLC17196MTBLC17053MTBLC16347MTBLC17895MTBLC7916MTBLC16870MTBLC16856MTBLC17858MTBLC16977MTBLC17553MTBLC18050MTBLC16015MTBLC17562MTBLC16027MTBLC17345MTBLC16761MTBLC1673226055719CHEBI:16010CHEBI:15603CHEBI:17191CHEBI:17196CHEBI:17053CHEBI:16347CHEBI:17895CHEBI:7916CHEBI:16870CHEBI:16856CHEBI:17858CHEBI:16977CHEBI:17553CHEBI:18050CHEBI:16015CHEBI:17562CHEBI:16027CHEBI:17345CHEBI:16761CHEBI:16732