Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Study Population and Sample Collection
4.2. Sample Collection
4.3. Sample Extraction and LC-MS/MS Mass Spectrometry
4.4. Feature-Based Molecular Networking Using GNPS and Compound Annotation
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Discovery Group | Validation Group | |||||
---|---|---|---|---|---|---|
Parameter | Cases | Controls | p-Value | Cases | Controls | p-Value |
Number of patients | 30 | 30 | 20 | 20 | ||
Age, mean (SD) | 25.7 (5.9) | 26.1 (6.7) | 0.147 ^ | 26.7 (5.2) | 25.1 (5.7) | 0.647 ^ |
Nullipara, n | 13 | 16 | 0.343 * | 18 | 22 | 0.248 * |
BMI, mean (SD) | 27.2 (5.3) | 26.1 (5.9) | 0.865 ^ | 25.2 (5.5) | 25.1 (4.9) | 0.955 ^ |
Risk Factors, n | ||||||
Previous EP | 6 | 3 | 0.044 * | 4 | 1 | 0.025 * |
Previous Adnexal Surgery | 7 | 3 | 0.046 * | 5 | 2 | 0.038 * |
Previous pelvic /abdominal Surgery | 8 | 10 | 0.423 * | 6 | 7 | 0.263 * |
History of Infertility | 3 | 4 | 0.520 * | 1 | 4 | 0.608 * |
History of PID | 6 | 5 | 0.378 * | 1 | 2 | 0.198 * |
Smoking | 7 | 5 | 0.102 * | 8 | 9 | 0.092 * |
Compound Name | Annotation Level | Raw Formula | m/z [M + H]+ | Feature ID | EP vs. IUP | p-Value |
---|---|---|---|---|---|---|
D-erythro-Sphingosine | 1 | C18H37NO2 | 300.289 | 240 | Down | <0.0001 |
Sphingosine 1-phosphate | 1 | C18H38NO5P | 380.255 | 146 | Down | <0.0001 |
Oleoyl L-carnitine | 1 | C25H47NO4 | 426.357 | 84 | Down | <0.0001 |
Phe-Trp | 2 | C20H21N3O3 | 352.165 | 147 | Down | <0.0001 |
Docosenamide | 2 | C22H43NO | 338.341 | 356 | Down | <0.0001 |
Hexadecyl-2-O-(2E-butenoyl)-sn-glyceryl-3-phosphocholine | 3 | C28H56NO7P | 550.386 | 60 | Down | <0.0001 |
1-Arachidoyl-2-hydroxy-sn-glycero-3-phosphocholine | 3 | C28H58NO7P | 552.402 | 102 | Down | <0.0001 |
Palmitoyl ethanolamide | 3 | C18H37NO2 | 300.289 | 73 | Down | <0.0001 |
1,2-Di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine | 2 | PC(18:3(9Z,12Z,15Z)/ 18:3(9Z,12Z,15Z)) | 778.538 | 373 | Down | 0.0001 |
13-ketooctadecadienoic acid | 3 | C18H30O3 | 295.226 | 89 | Up | 0.0001 |
N-Tetracosanoyl-4-sphingenyl-1-O-phosphorylcholine | 3 | C41H83N2O6P | 815.697 | 328 | Down | 0.0003 |
Tryptophan betaine | 3 | C14H18N2O2 | 247.143 | 43 | Down | 0.0009 |
7b,9-Dihydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-5-oxo-1,1a,1b,4,4a,5,7a,7b,8,9-decahydro-9ah-cyclopropa[3,4]benzo[1,2-e]azulen-9a-yl acetate | 1 | C22H30O6 | 432.238 | 432 | Up | 0.0012 |
1-Hexadecyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine | 3 | C42H84NO7P | 746.606 | 544 | Down | 0.0019 |
N-Methyl-L-tryptophan | 3 | C12H14N2O2 | 188.070 | 98 | Down | 0.0027 |
N-hexadecanoyl-D-erythro-sphingosine | 1 | C34H67NO3 | 274.274 | 85 | Down | 0.0032 |
Glycodeoxycholic acid | 1 | C26H43NO5 | 450.321 | 41 | Up | 0.0065 |
1-Stearoyl-2-hydroxy-sn-glycero-3-phosphocholine | 2 | C26H54NO7P | 524.371 | 3 | Down | 0.0158 |
Sphingomyelin (d18:1/24:0) | 2 | SM (d18:1/24:0) | 814.688 | 542 | Down | 0.0199 |
1-Octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine | 3 | PC (18:0/18:1) | 810.597 | 488 | Down | 0.0251 |
N-Lauroyl-D-erythro-sphingosylphosphorylcholine | 2 | 12:0 SM (d18:1/12:0) | 647.512 | 242 | Down | 0.0259 |
Metabolite Algorithms | AUC (95% CI) | Sensitivity | Specificity |
---|---|---|---|
D-erythro-C18-Sphingosine + Oleoyl L-carnitine | 0.962 (0.910–1.000) | 100% | 95.9% |
Palmitoyl ethanolamide + D-erythro-C18-Sphingosine | 0.963 (0.914–1.000) | 98.0% | 94.0% |
N-Palmitoylethanolamine + D-erythro-C18-Sphingosine + Sphingosine 1-phosphate + Phenylalanyl tryptophan | 0.955 (0.902–1.000) | 92.0% | 98.0% |
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Turkoglu, O.; Citil, A.; Katar, C.; Mert, I.; Quinn, R.A.; Bahado-Singh, R.O.; Graham, S.F. Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy. Int. J. Mol. Sci. 2024, 25, 10333. https://doi.org/10.3390/ijms251910333
Turkoglu O, Citil A, Katar C, Mert I, Quinn RA, Bahado-Singh RO, Graham SF. Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy. International Journal of Molecular Sciences. 2024; 25(19):10333. https://doi.org/10.3390/ijms251910333
Chicago/Turabian StyleTurkoglu, Onur, Ayse Citil, Ceren Katar, Ismail Mert, Robert A. Quinn, Ray O. Bahado-Singh, and Stewart F. Graham. 2024. "Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy" International Journal of Molecular Sciences 25, no. 19: 10333. https://doi.org/10.3390/ijms251910333
APA StyleTurkoglu, O., Citil, A., Katar, C., Mert, I., Quinn, R. A., Bahado-Singh, R. O., & Graham, S. F. (2024). Untargeted Metabolomic Biomarker Discovery for the Detection of Ectopic Pregnancy. International Journal of Molecular Sciences, 25(19), 10333. https://doi.org/10.3390/ijms251910333