Summary of Study ST002183
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001390. The data can be accessed directly via it's Project DOI: 10.21228/M82117 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002183 |
| Study Title | Individualized exercise intervention for people with multiple myeloma improves quality of life in a randomized controlled trial |
| Study Summary | Although new treatments have improved survival for multiple myeloma (MM), quality of life remains poor for people with this incurable cancer. We conducted a multi-site randomized, waitlist-controlled trial of an individualized exercise program for people at all stages of MM (n=60). Compared to the waitlist control group, participants of the 12-week intervention had significant improvement in health-related quality of life, mediated through improved MM symptoms, cardiorespiratory fitness and bone pain, with were mostly maintained at follow-up (up to 12 months). Exploratory plasma metabolomics and lipidomics was conducted to delineate molecular mechanisms and biomarkers |
| Institute | QIMR Berghofer Medical Research Institute |
| Laboratory | Precision & Systems Biomedicine |
| Last Name | Stoll |
| First Name | Thomas |
| Address | 300 Herston Road |
| thomas.stoll@qimrberghofer.edu.au | |
| Phone | +61 7 3845 3992 |
| Submit Date | 2022-06-01 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-05 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001390 |
| Project DOI: | doi: 10.21228/M82117 |
| Project Title: | Individualized exercise intervention for people with multiple myeloma improves quality of life in a randomized controlled trial |
| Project Type: | MS untargeted metabolomics analysis |
| Project Summary: | Although new treatments have improved survival for multiple myeloma (MM), quality of life remains poor for people with this incurable cancer. We conducted a multi-site randomized, waitlist-controlled trial of an individualized exercise program for people at all stages of MM (n=60). Compared to the waitlist control group, participants of the 12-week intervention had significant improvement in health-related quality of life, mediated through improved MM symptoms, cardiorespiratory fitness and bone pain, with were mostly maintained at follow-up (up to 12 months). Exploratory plasma metabolomics and lipidomics was conducted to delineate molecular mechanisms and biomarkers |
| Institute: | QIMR Berghofer Medical Research Institute |
| Laboratory: | Precision & Systems Biomedicine |
| Last Name: | Stoll |
| First Name: | Thomas |
| Address: | 300 Herston Road, Herston, Queensland, 4006, Australia |
| Email: | thomas.stoll@qimrberghofer.edu.au |
| Phone: | +61 7 3845 3992 |
Subject:
| Subject ID: | SU002269 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Group | Time_point |
|---|---|---|---|
| SA209692 | HP_BlankNegControlExtraction_04 | Blank | Blank |
| SA209693 | HP_BlankNegControlExtraction_03 | Blank | Blank |
| SA209694 | HP_BlankNegControlExtraction_01 | Blank | Blank |
| SA209695 | HP_BlankNegControlExtraction_06 | Blank | Blank |
| SA209696 | HP_BlankNegControlExtraction_02 | Blank | Blank |
| SA209697 | HP_BlankNegControlExtraction_05 | Blank | Blank |
| SA209746 | MM036_0_pE1 | exercise | - |
| SA209747 | MM055_0_pE1 | exercise | - |
| SA209748 | MM040_0_pE1 | exercise | - |
| SA209749 | MM051_0_pE1 | exercise | - |
| SA209750 | MM050_0_pE1 | exercise | - |
| SA209751 | MM044_0_pE1 | exercise | - |
| SA209752 | MM039_0_pE1 | exercise | - |
| SA209753 | MM032_0_pE1 | exercise | - |
| SA209754 | MM058_0_pE1 | exercise | - |
| SA209755 | MM041_0_pE1 | exercise | - |
| SA209756 | MM035_0_pE1 | exercise | - |
| SA209757 | MM022_0_pE1 | exercise | - |
| SA209758 | MM003_0_p1 | exercise | - |
| SA209759 | MM014_0_p1 | exercise | - |
| SA209760 | MM008_0_p1 | exercise | - |
| SA209761 | MM011_0_p1 | exercise | - |
| SA209762 | MM004_0_p1 | exercise | - |
| SA209763 | MM010_0_p1 | exercise | - |
| SA209764 | MM027_0_pE1 | exercise | - |
| SA209765 | MM026_0_pE1 | exercise | - |
| SA209766 | MM058_1_pE1 | exercise | 1 |
| SA209767 | MM051_1_pE1 | exercise | 1 |
| SA209768 | MM050_1_pE1 | exercise | 1 |
| SA209769 | MM036_1_pE1 | exercise | 1 |
| SA209770 | MM055_1_pE1 | exercise | 1 |
| SA209771 | MM041_1_pE1 | exercise | 1 |
| SA209772 | MM044_1_pE1 | exercise | 1 |
| SA209773 | MM040_1_pE1 | exercise | 1 |
| SA209774 | MM039_1_pE1 | exercise | 1 |
| SA209775 | MM022_1_pE1 | exercise | 1 |
| SA209776 | MM008_1_pE1 | exercise | 1 |
| SA209777 | MM010_1_pE1 | exercise | 1 |
| SA209778 | MM032_1_pE1 | exercise | 1 |
| SA209779 | MM014_1_pE1 | exercise | 1 |
| SA209780 | MM011_1_pE1 | exercise | 1 |
| SA209781 | MM035_1_pE1 | exercise | 1 |
| SA209782 | MM027_1_pE1 | exercise | 1 |
| SA209783 | MM003_1_pE1 | exercise | 1 |
| SA209784 | MM026_1_pE1 | exercise | 1 |
| SA209785 | MM004_1_pE1 | exercise | 1 |
| SA209786 | MM027_3_pE1 | exercise | 3 |
| SA209787 | MM036_3_pE1 | exercise | 3 |
| SA209788 | MM022_3_pE1 | exercise | 3 |
| SA209789 | MM014_3_pE1 | exercise | 3 |
| SA209790 | MM026_3_pE1 | exercise | 3 |
| SA209791 | MM011_3_pE1 | exercise | 3 |
| SA209792 | MM004_3_pE1 | exercise | 3 |
| SA209793 | MM035_3_pE1 | exercise | 3 |
| SA209794 | MM003_3_pE1 | exercise | 3 |
| SA209795 | MM008_3_pE1 | exercise | 3 |
| SA209796 | MM010_3_pE1 | exercise | 3 |
| SA209698 | QC_HP_itMS2_CE0_it08 | MS2 | MS2 |
| SA209699 | QC_HP_itMS2_CE0_it07 | MS2 | MS2 |
| SA209700 | QC_HP_itMS2_CE0_it06 | MS2 | MS2 |
| SA209701 | QC_HP_itMS2_CE10_it01 | MS2 | MS2 |
| SA209702 | QC_HP_itMS2_CE10_it02 | MS2 | MS2 |
| SA209703 | QC_HP_itMS2_CE10_it04 | MS2 | MS2 |
| SA209704 | QC_HP_itMS2_CE10_it03 | MS2 | MS2 |
| SA209705 | QC_HP_itMS2_CE0_it05 | MS2 | MS2 |
| SA209706 | QC_HP_itMS2_CE0_it04 | MS2 | MS2 |
| SA209707 | QC_HP_itMS2_CE40_it06 | MS2 | MS2 |
| SA209708 | QC_HP_itMS2_CE40_it04 | MS2 | MS2 |
| SA209709 | QC_HP_itMS2_CE40_it08 | MS2 | MS2 |
| SA209710 | QC_HP_itMS2_CE40_it05 | MS2 | MS2 |
| SA209711 | QC_HP_itMS2_CE0_it01 | MS2 | MS2 |
| SA209712 | QC_HP_itMS2_CE0_it03 | MS2 | MS2 |
| SA209713 | QC_HP_itMS2_CE0_it02 | MS2 | MS2 |
| SA209714 | QC_HP_itMS2_CE10_it05 | MS2 | MS2 |
| SA209715 | QC_HP_itMS2_CE40_it07 | MS2 | MS2 |
| SA209716 | QC_HP_itMS2_CE20_it06 | MS2 | MS2 |
| SA209717 | QC_HP_itMS2_CE20_it05 | MS2 | MS2 |
| SA209718 | QC_HP_itMS2_CE20_it04 | MS2 | MS2 |
| SA209719 | QC_HP_itMS2_CE20_it07 | MS2 | MS2 |
| SA209720 | QC_HP_itMS2_CE20_it08 | MS2 | MS2 |
| SA209721 | QC_HP_itMS2_CE40_it02 | MS2 | MS2 |
| SA209722 | QC_HP_itMS2_CE40_it01 | MS2 | MS2 |
| SA209723 | QC_HP_itMS2_CE20_it03 | MS2 | MS2 |
| SA209724 | QC_HP_itMS2_CE40_it03 | MS2 | MS2 |
| SA209725 | QC_HP_itMS2_CE10_it07 | MS2 | MS2 |
| SA209726 | QC_HP_itMS2_CE10_it06 | MS2 | MS2 |
| SA209727 | QC_HP_itMS2_CE20_it01 | MS2 | MS2 |
| SA209728 | QC_HP_itMS2_CE10_it08 | MS2 | MS2 |
| SA209729 | QC_HP_itMS2_CE20_it02 | MS2 | MS2 |
| SA209730 | QC_HP_10 | QC | QC |
| SA209731 | QC_HP_07 | QC | QC |
| SA209732 | QC_HP_08 | QC | QC |
| SA209733 | QC_HP_09 | QC | QC |
| SA209734 | QC_HP_06 | QC | QC |
| SA209735 | QC_HP_04 | QC | QC |
| SA209736 | QC_HP_01 | QC | QC |
| SA209737 | QC_HP_02 | QC | QC |
| SA209738 | QC_HP_03 | QC | QC |
| SA209739 | QC_HP_11 | QC | QC |
| SA209740 | QC_HP_05 | QC | QC |
Collection:
| Collection ID: | CO002262 |
| Collection Summary: | Fasted plasma samples were collected from participants at multiple time points as depicted in Figure 1, taken from the protocol paper Nicol, J.L.;Woodrow, C.;Cunningham, B.J.; Mollee, P.;Weber, N.; Smith, M.D.; Nicol, A.J.; Gordon, L.G.; Hill, M.M.; Skinner, T.L. An Individualized Exercise Intervention for People with Multiple Myeloma—Study Protocol of a Randomized Waitlist-Controlled Trial. Curr. Oncol. 2022, 29, 901–923. https://doi.org/10.3390/curroncol29020077. After overnight fasting, plasma was collected by an experienced phlebotomist from an antecubital vein using a 23-gauge needle into EDTA-coated blood collection tubes and immediately stored on ice. Aliquots were prepared in Eppendorf tubes within 4 hours, and frozen at -80oC until use |
| Sample Type: | Blood (plasma) |
Treatment:
| Treatment ID: | TR002281 |
| Treatment Summary: | Multiple myeloma patients were randomized to exercise (EX) or waitlist (WT) groups as detailed in the protocol paper: Nicol, J.L.;Woodrow, C.;Cunningham, B.J.; Mollee, P.;Weber, N.; Smith, M.D.; Nicol, A.J.; Gordon, L.G.; Hill, M.M.; Skinner, T.L. An Individualized Exercise Intervention for People with Multiple Myeloma—Study Protocol of a Randomized Waitlist-Controlled Trial. Curr. Oncol. 2022, 29, 901–923. https://doi.org/10.3390/curroncol29020077. The individualized exercise program was for 3 months, and follow-up plasma was collected at 12 months. WT group had usual care for 3 months prior to the same exercise and follow-up regime |
Sample Preparation:
| Sampleprep ID: | SP002275 |
| Sampleprep Summary: | In total, 126 human plasma samples from 46 patients were prepared. All samples (including QCs and blanks) were randomized in one batch and then evenly split between two 2 mL 96-deepwell plates (Eppendorf #0030 501.306). Human plasma samples were thawed on ice and briefly vortexed before aliquoting 100 µL plasma of each sample to a well. In addition, a global sample pool containing equal volumes (12 µL) of each sample was prepared into a 2 mL Eppendorf tube as quality control (QC) and 12 x 100 µL aliquots were transferred into wells across the 2 plates. Finally, blank negative control extraction samples were prepared by transferring 100 µL of 1X PBS to 6 wells equally across 2 plates. Ten-times the sample volume of ice-cold butanol/methanol (1:1) containing 50 µg/mL antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT) and 0.5 µg/mL ISTD 4-chloro-L-phenylalanine (PCPA) was added to each well using a multi-channel pipette. Plates were covered with organic solvent resistant sealing mats (Eppendorf #0030 127.960) and vortexed for 3 min at 1000 rpm. Samples were then sonicated for 15 min in an ice-cold water bath sonicator, stored overnight at -30oC and centrifuged for 30 min at 4,000 x g (4oC). Samples were aliquoted into 96-well V-bottom plates (Greiner #651201) using a liquid handler platform (AssayMap Bravo, Agilent). From each deepwell plate, 4 x 100 µL and 2 x 200 µL aliquots were prepared, totalling 8 and 4 plates, respectively. Samples were dried down (2.5 hrs) using a Genevac EZ-2 vacuum concentrator and fast-stack swings facilitating drying of 8 plates per batch. Dried sample plates were covered with AlumaSeal CS sealing film for cold storage (Finneran-Porviar #FC-100) and stored at -80oC until LC/MS analysis |
Combined analysis:
| Analysis ID | AN003575 | AN003576 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | HILIC |
| Chromatography system | Agilent 1290 Infinity II | Agilent 1290 Infinity II |
| Column | Agilent ZORBAX RRHD Eclipse Plus C18 (50 x 2.1 mm,1.8 µm | Agilent Poroshell 120 HILIC-Z (100 2.1mm,2.7um) |
| MS Type | ESI | ESI |
| MS instrument type | QTOF | QTOF |
| MS instrument name | Agilent 6545 QTOF | Agilent 6545 QTOF |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | peak area | peak area |
Chromatography:
| Chromatography ID: | CH002643 |
| Chromatography Summary: | Reversed-phase separation of metabolites was adapted from Evans et al. (2014) with modifications. Separation was achieved on a Zorbax Eclipse Plus C18 RRHD (1.8 μm, 95 Å, 2.1x50mm, #959757-902, Agilent) column held at 40°C and the MS was operated in positive ionization mode. Eluent A was milliQ water and eluent B was methanol both containing 0.1% formic acid. Total method runtime was 8.5 min with the following gradient: 0 min (0.5% eluent B) – 4 min (70% B) – 4.5 min (98% B) – 5.4 min (98% B) – 5.5 min (0.5% B) – 8.5 min (0.5% B). The flow was diverted to waste after 5 minutes and a flow rate of 0.4 mL/min was applied |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Agilent ZORBAX RRHD Eclipse Plus C18 (50 x 2.1 mm,1.8 µm |
| Column Temperature: | 40 |
| Flow Gradient: | 0 min (0.5% eluent B) - 4 min (70% B) - 4.5 min (98% B) - 5.4 min (98% B) - 5.5 min (0.5% B) - 8.5 min (0.5% B). The flow was diverted to waste after 5 minutes |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% methanol; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH002644 |
| Chromatography Summary: | HILIC separation of metabolites was carried out on a Poroshell 120 HILIC-Z (100Å, 2.7µm, 2.1x100mm, #675775-924, Agilent) column at 30ºC and the MS was operated in negative ionization mode. Eluent A was 10 mM ammonium acetate and 5 μM medronic acid in ACN/milliQ 90:10 (pH 9) and eluent B was 10 mM ammonium acetate and 5 μM medronic acid in milliQ (pH 9). Gradient applied was: 0 min (10% eluent B) – 3.5 min (25% B) – 5.5 min (50% B) – 7.5 min (50% B) – 7.6 min (10% B) – 14 min (10% B). Flow rate was set to 0.25 mL/min with a flow ramp to 0.5 mL/min during equilibration |
| Instrument Name: | Agilent 1290 Infinity II |
| Column Name: | Agilent Poroshell 120 HILIC-Z (100 2.1mm,2.7um) |
| Flow Gradient: | Gradient applied was: 0 min (10% eluent B) - 3.5 min (25% B) - 5.5 min (50% B) - 7.5 min (50% B) - 7.6 min (10% B) - 14 min (10% B). |
| Flow Rate: | 0.25 mL/min |
| Solvent A: | 90% acetonitrile/10% water; 10 mM ammonium acetate; 5 µM medronic acid, pH 9 |
| Solvent B: | 100% water; 10 mM ammonium acetate; 5 µM medronic acid, pH 9 |
| Chromatography Type: | HILIC |
MS:
| MS ID: | MS003332 |
| Analysis ID: | AN003575 |
| Instrument Name: | Agilent 6545 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | MS acquisition: Full scan MS data acquisition (m/z 50-1700) was carried out at a scan rate of 2.5 spectra/sec with the following source conditions applied for metabolites analysed on reversed-phase: Gas temperature 250°C, gas flow 13 L/min, sheath gas temperature and flow at 400°C and 12 L/min, respectively, nebulizer 30 psi, fragmentor 135, capillary voltage at +4500 V, nozzle voltage and CE were zero. For metabolite separation on HILIC conditions were adjusted as follows: Gas temperature 200°C, gas flow 10 L/min, nebulizer 40 psi, capillary voltage at -2500 V. MS/MS acquisition: For compound identification, the ‘Iterative MS/MS’ data acquisition mode was employed, i.e. a sample (here: QC pools) was injected multiple times and precursors previously selected for MS/MS fragmentation were excluded in subsequent runs. Eight iterative MS/MS acquisition runs per fixed collision energy (CE) value were performed with CE values set to 0, 10, 20, and 40 V. Spectral parameters were as follows: MS and MS/MS mass range was 50-1700; MS and MS/MS acquisition rate was 3 spectra/sec; quadrupole isolation width was narrow (~1.3 m/z). A maximum of 8 precursors per cycle were targeted which resulted in a cycle time of 3.1 s. Precursor threshold was set to 500 counts or 0.001% with an active exclusion of 0.2 min after 1 spectra. Iterative MS/MS settings were enabled with a mass error tolerance of +/- 5 ppm and retention time exclusion tolerance of +/- 0.1 min. Precursor charge state was set to 1, 2 and unknown. Precursor abundance-based scan speed with a target of 25,000 counts/spectrum and the use MS/MS accumulation time limit were enabled. Precursor purity stringency was kept at 70% and cutoff 0%. Reference ions were excluded from fragmentation with a delta mass tolerance of 10 ppm. Data processing: Feature extraction was performed separately for each of the 2 LC/MS analysis modes. A total of 148 data files (126 patient samples, 16 QCs, and 6 blank negative control extractions) were loaded into MassHunter Profinder (v 10 SP1, Agilent) and assigned to sample groups. Patient samples were divided into 2 sample groups (waitlist and exercise group), totalling 4 samples groups altogether. First, retention time alignment was conducted using a QC run as reference file. Spectral feature extraction was then performed using the recursive feature extraction method employing default settings with minor adjustments: Peak extraction retention time (Rt) range was restricted to 0.1-5 min and 0.1-7 min for reversed-phase and HILIC, respectively, compound binning and alignment tolerances were set to 1% + 0.3 min for Rt and 20 ppm + 2 mDa for mass, integrator Agile 2 was used for peak integration, peak filters were set to at least 2500 counts and features must have satisfied filter conditions in at least 75 % of files in at least one sample group. Feature peak area was exported and data cleaning was performed in accordance with Southam et al. (2021) using an in-house R script compiled of the following steps. QC samples were removed from the data matrix area if the total peak area (of all features) exceeded +/-25% of the median QC total peak area. Features were deleted from the data matrix if: detected in less than 70% of QC samples; absent across all sample groups; the mean QC/extract blank area ratio was less than 5; and the peak area RSD across QC samples was larger than 30%. In addition, duplicate feature entries were removed. |
| Ion Mode: | POSITIVE |
| MS ID: | MS003333 |
| Analysis ID: | AN003576 |
| Instrument Name: | Agilent 6545 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | MS acquisition: Full scan MS data acquisition (m/z 50-1700) was carried out at a scan rate of 2.5 spectra/sec with the following source conditions applied for metabolites analysed on reversed-phase: Gas temperature 250°C, gas flow 13 L/min, sheath gas temperature and flow at 400°C and 12 L/min, respectively, nebulizer 30 psi, fragmentor 135, capillary voltage at +4500 V, nozzle voltage and CE were zero. For metabolite separation on HILIC conditions were adjusted as follows: Gas temperature 200°C, gas flow 10 L/min, nebulizer 40 psi, capillary voltage at -2500 V. MS/MS acquisition: For compound identification, the ‘Iterative MS/MS’ data acquisition mode was employed, i.e. a sample (here: QC pools) was injected multiple times and precursors previously selected for MS/MS fragmentation were excluded in subsequent runs. Eight iterative MS/MS acquisition runs per fixed collision energy (CE) value were performed with CE values set to 0, 10, 20, and 40 V. Spectral parameters were as follows: MS and MS/MS mass range was 50-1700; MS and MS/MS acquisition rate was 3 spectra/sec; quadrupole isolation width was narrow (~1.3 m/z). A maximum of 8 precursors per cycle were targeted which resulted in a cycle time of 3.1 s. Precursor threshold was set to 500 counts or 0.001% with an active exclusion of 0.2 min after 1 spectra. Iterative MS/MS settings were enabled with a mass error tolerance of +/- 5 ppm and retention time exclusion tolerance of +/- 0.1 min. Precursor charge state was set to 1, 2 and unknown. Precursor abundance-based scan speed with a target of 25,000 counts/spectrum and the use MS/MS accumulation time limit were enabled. Precursor purity stringency was kept at 70% and cutoff 0%. Reference ions were excluded from fragmentation with a delta mass tolerance of 10 ppm. Data processing: Feature extraction was performed separately for each of the 2 LC/MS analysis modes. A total of 148 data files (126 patient samples, 16 QCs, and 6 blank negative control extractions) were loaded into MassHunter Profinder (v 10 SP1, Agilent) and assigned to sample groups. Patient samples were divided into 2 sample groups (waitlist and exercise group), totalling 4 samples groups altogether. First, retention time alignment was conducted using a QC run as reference file. Spectral feature extraction was then performed using the recursive feature extraction method employing default settings with minor adjustments: Peak extraction retention time (Rt) range was restricted to 0.1-5 min and 0.1-7 min for reversed-phase and HILIC, respectively, compound binning and alignment tolerances were set to 1% + 0.3 min for Rt and 20 ppm + 2 mDa for mass, integrator Agile 2 was used for peak integration, peak filters were set to at least 2500 counts and features must have satisfied filter conditions in at least 75 % of files in at least one sample group. Feature peak area was exported and data cleaning was performed in accordance with Southam et al. (2021) using an in-house R script compiled of the following steps. QC samples were removed from the data matrix area if the total peak area (of all features) exceeded +/-25% of the median QC total peak area. Features were deleted from the data matrix if: detected in less than 70% of QC samples; absent across all sample groups; the mean QC/extract blank area ratio was less than 5; and the peak area RSD across QC samples was larger than 30%. In addition, duplicate feature entries were removed. |
| Ion Mode: | NEGATIVE |
