LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage
Abstract Sepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understan...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
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| Series: | European Journal of Medical Research |
| Online Access: | https://doi.org/10.1186/s40001-023-01612-7 |
| _version_ | 1797350065624317952 |
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| author | Pär I. Johansson Hanne H. Henriksen Sigurður T. Karvelsson Óttar Rolfsson Martin Schønemann-Lund Morten H. Bestle Sarah McGarrity |
| author_facet | Pär I. Johansson Hanne H. Henriksen Sigurður T. Karvelsson Óttar Rolfsson Martin Schønemann-Lund Morten H. Bestle Sarah McGarrity |
| author_sort | Pär I. Johansson |
| collection | DOAJ |
| description | Abstract Sepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understand the risk factors would allow better treatment targeting. Sepsis causes metabolic dysregulation in patients; therefore, metabolomics offers a promising tool to study sepsis. It is also known that that in sepsis endothelial cells affecting their function regarding blood clotting and vascular permeability. We integrated metabolomics data from patients admitted to an intensive care unit for sepsis, with commonly collected clinical features of their cases and two measures of endothelial function relevant to blood vessel function, platelet endothelial cell adhesion molecule and soluble thrombomodulin concentrations in plasma. We used least absolute shrinkage and selection operator penalized regression, and pathway enrichment analysis to identify features most able to predict 30-day survival. The features important to sepsis survival include carnitines, and amino acids. Endothelial proteins in plasma also predict 30-day mortality and the levels of these proteins also correlate with a somewhat overlapping set of metabolites. Overall metabolic dysregulation, particularly in endothelial cells, may be a contributory factor to sepsis response. By exploring sepsis metabolomics data in conjunction with clinical features and endothelial proteins we have gained a better understanding of sepsis risk factors. |
| first_indexed | 2024-03-08T12:39:27Z |
| format | Article |
| id | doaj.art-738699080381430d9b45ae0de27a6d7f |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-08T12:39:27Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-738699080381430d9b45ae0de27a6d7f2024-01-21T12:14:57ZengBMCEuropean Journal of Medical Research2047-783X2024-01-0129111410.1186/s40001-023-01612-7LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damagePär I. Johansson0Hanne H. Henriksen1Sigurður T. Karvelsson2Óttar Rolfsson3Martin Schønemann-Lund4Morten H. Bestle5Sarah McGarrity6CAG Center for Endotheliomics, Copenhagen University Hospital - RigshospitaletCAG Center for Endotheliomics, Copenhagen University Hospital - RigshospitaletBiomedical Center, University of IcelandBiomedical Center, University of IcelandDepartment of Anaesthesiology and Intensive Care, Copenhagen University Hospital - North ZealandDepartment of Clinical Medicine, University of CopenhagenBiomedical Center, University of IcelandAbstract Sepsis is a major cause of death worldwide, with a mortality rate that has remained stubbornly high. The current gold standard of risk stratifying sepsis patients provides limited mechanistic insight for therapeutic targeting. An improved ability to predict sepsis mortality and to understand the risk factors would allow better treatment targeting. Sepsis causes metabolic dysregulation in patients; therefore, metabolomics offers a promising tool to study sepsis. It is also known that that in sepsis endothelial cells affecting their function regarding blood clotting and vascular permeability. We integrated metabolomics data from patients admitted to an intensive care unit for sepsis, with commonly collected clinical features of their cases and two measures of endothelial function relevant to blood vessel function, platelet endothelial cell adhesion molecule and soluble thrombomodulin concentrations in plasma. We used least absolute shrinkage and selection operator penalized regression, and pathway enrichment analysis to identify features most able to predict 30-day survival. The features important to sepsis survival include carnitines, and amino acids. Endothelial proteins in plasma also predict 30-day mortality and the levels of these proteins also correlate with a somewhat overlapping set of metabolites. Overall metabolic dysregulation, particularly in endothelial cells, may be a contributory factor to sepsis response. By exploring sepsis metabolomics data in conjunction with clinical features and endothelial proteins we have gained a better understanding of sepsis risk factors.https://doi.org/10.1186/s40001-023-01612-7 |
| spellingShingle | Pär I. Johansson Hanne H. Henriksen Sigurður T. Karvelsson Óttar Rolfsson Martin Schønemann-Lund Morten H. Bestle Sarah McGarrity LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage European Journal of Medical Research |
| title | LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| title_full | LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| title_fullStr | LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| title_full_unstemmed | LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| title_short | LASSO regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| title_sort | lasso regression shows histidine and sphingosine 1 phosphate are linked to both sepsis mortality and endothelial damage |
| url | https://doi.org/10.1186/s40001-023-01612-7 |
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