Computational Medicine Group

News

We have been awarded by the SNSF as "project partner" in the COVID19-project 31CA30_196059 / 1 of Guido Beldi et al. (link).

Our manuscript "Time requirement and feasibility of a systematic quality peer review of reporting in radiology" has been accepted at RöFo. More soon!

We have been kindly awarded with a grant for our Project "PGXLink PGM (PharmacoGenoMetabolomics)" from the Bern Center of Precision Medicine (BCPM). More soon!

In the actual issue of the Pipette, we present a short overview on "Präanalytik - Chancen durch Digitalisierung".

We have been kindly mentioned in an upcoming article of the Revue suisse d'histoire religieuse et culturelle (off topic).

We welcome our new MSc Bioinformatics Student Harald Witte for a joint Project with Prof. L. Bally (Diabetology).

 

We have been awarded with generous funding by the SPHN and SNSF!

Update 2019-11-22: We received also a SNSF SPARK grant (PI Andrew Atkinson) of 100'000 CHF.

 

 

 

3-dimensional ROC corve for high-seinsitive Troponin T (cf. Haider et al. High sensitive cardiac troponin T: Testing the test. Int J Cardiol. 2017;228:779-783)

This site is regularly updated.

Date of last change: May 20th, 2020

Computational Medicine

Computational Medicine is a new field of medicine at the interface between data generating (mainly diagnostic) medical disciplines (e.g. "-omics")  and data science (informatics, statistics). It provides information on patients, their health and underlying processes and pathways by exhaustive computational and statistical methodology, that exceed the capacities of conventional approaches.

Computational medicine tries to generate and assess models from existing data to predict/classify/diagnose new patients. It uses large-scale standard modeling approaches (GLMs, GEEs &c.), but also "deep" machine learning and digitally resembles complex decision-finding processes that today depend on physician's experience, knowledge, and intuition.

What we do

  • Predictive modeling of clinically relevant outcomes from laboratory data
  • Deep evaluation of “-omics” data, especially Metabolomics
  • Develop and apply tools for laboratory medicine
  • Computational/statistical support for clinical studies involving “big data”

Lead

Alexander Leichtle
Leitender Akademiker
Tel.+41 31 632 83 30E-Mail G  

Researchers and Fellows

Research Fellow and Consultant:
Prof. Christos T. Nakas, also Director of the Laboratory of Biometry, University of Thessaly, Volos, Greece.

 

 

Former members

Nazanin Sédille-Mostafaie (2017-2019)

Students

  • Harald Witte (MSc Bioinformatics)
  • Zara Liniger (MD thesis)
  • Nadine Sägesser (MD Thesis)

Alumni

  • Stefan Zahnd (Master Bioinformatics)
  • Zara Liniger (Master Medicine)
  • Marcia Heinzmann (Master Medicine)
  • Narayan Schütz (Master Bioinformatics)
  • Daniel Lienhard (Master Bioinformatics)
  • Nenad Torbica (Master Bioinformatics)

GitHub Repositories

Our group hosts GitHub repositories:

  

Publications

Publications of our team

2020

  • Freiburghaus K*, Leichtle AB*, Nakas CT, Fiedler GM, Largiadèr CR. Effects of Freezing and Thawing Procedures on Selected Clinical Chemistry Parameters in Plasma. Biopreservation and Biobanking. 2020. doi:10.1089/bio.2020.0005
  • Franco‐Pereira AM, Nakas CT, Athanassiou CG, Pardo MC. Testing against umbrella or tree orderings for binomial proportions with an adaptation of an insect resistance case. Biometrical Journal. 2020. doi:10.1002/bimj.201900272
  • Musy SN, Endrich O, Leichtle AB, Griffiths P, Nakas CT, Simon M. Longitudinal Study of the Variation in Patient Turnover and Patient-to-Nurse Ratio: Descriptive Analysis of a Swiss University Hospital
    J Med Internet Res 2020;22(4):e15554, DOI: 10.2196/15554, PMID: 32238331
  • Arnold M, Nakas C, Luft A, Christ-Crain M, Leichtle A, Katan M. Independent Prognostic Value of MRproANP (Midregional Proatrial Natriuretic Peptide) Levels in Patients With Stroke Is Unaltered Over Time. Stroke. 2020; doi:10.1161/STROKEAHA.120.029333, PMID: 32216532
  • Herzig D, Nakas CT, Stalder J, Kosinski C, Laesser C, Dehais J, Jaeggi R, Leichtle AB, Dahlweid FM, Stettler C, Bally L. Volumetric Food Quantification Using Computer Vision on a Depth-Sensing Smartphone: Preclinical Study. JMIR Mhealth Uhealth 2020;8(3):e15294, DOI: 10.2196/15294, PMID: 32209531
  • Herzig D, Dehais J, Prost JC, Nakas CT, Stettler C, Bally L, Hovorka R. Pharmacokinetics of faster and standard insulin aspart during fully closed-loop insulin delivery in type 2 diabetes. Diabetes Technology & Therapeutics. http://doi.org/10.1089/dia.2019.0477
  • Schefold JC, Gerber JL, Angehrn MC, Müller M, Messmer AS, Leichtle AB, Fiedler GM, Exadaktylos AK, Pfortmueller CA. Renal Function-Adjusted D-Dimer Levels in Critically Ill Patients With Suspected Thromboembolism. Crit Care Med. 2020 . doi: 10.1097/CCM.0000000000004204. PMID: 31913987
  • Rindlisbacher B, Schild C, Egger F, Bacher VU, Pabst T, Leichtle A, Andres M, Sédille-Mostafaie N, Serum Free Light Chain Assay: Shift Toward a Higher κ/λ Ratio, The Journal of Applied Laboratory Medicine, Volume 5, Issue 1, January 2020, Pages 114–125, https://doi.org/10.1093/jalm.2019.029330

 

2019

  • Noll S, Furrer R, Reiser B, Nakas CT. Inference in receiver operating characteristic surface analysis via a trinormal model‐based testing approach. Stat 2019, 8. https://doi.org/10.1002/sta4.249.
  • van Hoek J, Huber A, Leichtle A, Härmä K, Hilt D, von Tengg-Kobligk H, Heverhagen J, Poellinger A. A survey on the future of radiology among radiologists, medical students and surgeons: Students and surgeons tend to be more skeptical about artificial intelligence and radiologists may fear that other disciplines take over.Eur J Radiol. 2019; 121:108742. doi: 10.1016/j.ejrad.2019.108742. PMID: 31734640
  • Endrich O, Triep K, Torbica N, Nakas CT, Nelle M, Fiedler M, Raio L. Changepoint analysis of gestational age and birth weight: proposing a refinement of Diagnosis Related Groups. Pediatr Res. 2019. doi: 10.1038/s41390-019-0669-0. PMID: 31715621
  • Diamantidis AD, Ioannou CS, Nakas CT, Carey JR, Papadopoulos NT. Differential response to larval crowding of a long and a short lived medfly biotype. J Evol Biol. doi: 10.1111/jeb.13569. PMID: 31705603
  • Wolfensberger N, Georgiou G, Giabbani E, Reusser M, Njue LM, Fiedler M, Leichtle AB, Nagler M. Rapid Centrifugation in the Routine Hemostasis Laboratory. Thromb Haemost. 2019 Oct 10. doi: 10.1055/s-0039-1696712. PMID: 31600807
  • Egli-Spichtig D, Imenez Silva PH, Glaudemans B, Gehring N, Bettoni C, Zhang MYH, Pastor-Arroyo EM, Schönenberger D, Rajski M, Hoogewijs D, Knauf F, Misselwitz B, Frey-Wagner I, Rogler G, Ackermann D, Ponte B, Pruijm M, Leichtle A, Fiedler GM, Bochud M, Ballotta V, Hofmann S, Perwad F, Föller M, Lang F, Wenger RH, Frew I, Wagner CA. Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation. Kidney Int. 2019. pii: S0085-2538(19)30465-X. doi: 10.1016/j.kint.2019.04.009.  PMID: 31301888
  • Alonso R, Nakas CT, Pardo MC, A study of indices useful for the assessment of diagnostic markers in non-parametric ROC curve analysis. Communication in Statistics- Simulation and Computation 2019. DOI: 10.1080/03610918.2018.1511806
  • Scholz GA*, Leichtle AB*, Scherer A, Arndt U, Fiedler M, Aeberli D, Finckh A, Gabay C, Kyburz D, Villiger PM, Möller B. The links of hepcidin and erythropoietin in the interplay of inflammation and iron deficiency in a large observational study of rheumatoid arthritis. Br J Haematol 2019. doi: 10.1111/bjh.15895. PMID: 30941747
  • Schuh SK, Seidenberg R, Arampatzis S, Leichtle AB, Hautz WE, Exadaktylos AK,Schechter CB, Müller M. Diagnosis of Urinary Tract Infections by Urine Flow Cytometry: Adjusted Cut-Off Values in Different Clinical Presentations. Disease Markers 2019, https://doi.org/10.1155/2019/5853486.
  • Bantis LE, Nakas CT, Reiser B. Construction of confidence intervals for the maximum of the Youden index and the corresponding cutoff point of a continuous biomarker. Biom J. 2019 Jan;61(1):138-156. doi: 10.1002/bimj.201700107. PMID: 30408224

 

2018

  • Horn MP, Peter AM, Righini Grunder F, Leichtle AB, Spalinger J, Schibli S, Sokollik C. PR3-ANCA and panel diagnostics in pediatric inflammatory bowel disease to distinguish ulcerative colitis from Crohn's disease. PLoS One. 2018;13(12):e0208974. doi: 10.1371/journal.pone.0208974.PMID: 30557305
  • Dahlweid F-M, Kämpf M, Leichtle A. Interoperability of laboratory data in Switzerland – a spotlight on Bern. J Lab Med, 2018. https://doi.org/10.1515/labmed-2018-0072
  • Müller M, Schefold JC, Leichtle AB, Srivastava D, Lindner G, Exadaktylos AK, Pfortmueller CA. qSOFA score not predictive of in-hospital mortality in emergency patients with decompensated liver cirrhosis. Med Klin Intensivmed Notfmed, 2018. doi: 10.1007/s00063-018-0477-z. PMID: 30132026
  • von Wolff M, Nakas CT, Tobler M, Merz TM, Hilty MP, Veldhuis JD, Huber AR, Pichler Hefti J. Adrenal, thyroid and gonadal axes are affected at high altitude. Endocrine Connections, 2018. https://doi.org/10.1530/EC-18-0242
  • Walder A, Müller M, Dahdal S, Sidler D, Devetzis V, Leichtle AB, Fiedler MG, Popp AW, Lippuner K, Vogt B, Uehlinger D, Huynh-Do U, Arampatzis S. The effect of a previous created distal arteriovenous-fistula on radial bone DXA measurements in prevalent renal transplant recipients. PLoS One. 2018;13(7):e0200708. doi: 10.1371/journal.pone.0200708.
    PMID: 30048464
  • Findeisen P, Zahn I, Fiedler GM, Leichtle AB, Wang S, Soria G, Johnson P, Henzell J, Hegel JK, Bendavid C, Collet N, McGovern M, Klopprogge K. Doubling immunochemistry laboratory testing efficiency with the cobas e 801 module while maintaining consistency in analytical performance, Clinical Biochemistry 2018. https://www.sciencedirect.com/science/article/pii/S000991201731130X
  • Franco-Pereira AM, Nakas CT, Leichtle AB, Pardo MC. Bootstrap-based testing approaches for the assessment of the diagnostic accuracy of biomarkers subject to a limit of detection. Statistical Methods in Medical Research 2018, http://journals.sagepub.com/doi/full/10.1177/0962280218769334
  • Liu X, Hoene M, Yin P, Fritsche L, Plomgaard P, Hansen JS, Nakas CT, Niess AM, Hudemann J, Haap M, Mendy M, Weigert C, Wang X, Fritsche A, Peter A, Häring HU, Xu G, Lehmann R. Quality Control of Serum and Plasma by Quantification of (4E,14Z)-Sphingadienine-C18-1-Phosphate Uncovers Common Preanalytical Errors During Handling of Whole Blood. Clinical Chemistry 2018, clinchem.2017.277905; DOI: 10.1373/clinchem.2017.277905
  • Schütz N, Leichtle AB, & Riesen K.  A comparative study of pattern recognition algorithms for predicting the inpatient mortality risk using routine laboratory measurements .Artif Intell Rev (2018). https://doi.org/10.1007/s10462-018-9625-3
  • Müller M, Seidenberg R, Schuh SK, Exadaktylos AK, Schechter CB, Leichtle AB, Hautz WE. (2018) The development and validation of different decision-making tools to predict urine culture growth out of urine flow cytometry parameter. PLoS ONE 13(2): e0193255. https://doi.org/10.1371/journal.pone.0193255
  • Lesche D, Sigurdardottir V, Leichtle AB, Nakas CT, Christians U, Englberger L, Fiedler GM, Largiadèr CR, Mohacsi P, Sistonen J. Targeted and global pharmacometabolomics in everolimus-based immunosuppression: association of co-medication and lysophosphatidylcholines with dose requirement. Metabolomics (2018) 14: 3. https://doi.org/10.1007/s11306-017-1294-8
  • Cadamuro J, Mrazek C, Leichtle AB, Kipman U, Felder TK, Wiedemann H, Oberkofler H, Fiedler GM, Haschke-Becher E. Influence of centrifugation conditions on the results of 77 routine clinical chemistry analytes using standard vacuum blood collection tubes and the new BD-Barricor tubes. Biochem Med (Zagreb) 2018;28(1):010704, doi:10.11613/BM.2018.010704

 

2017

  • Müller M, Guignard V, Schefold JC, Leichtle AB, Exadaktylos AK, Pfortmueller CA. Utility of quick sepsis-related organ failure assessment (qSOFA) to predict outcome in patients with pneumonia. PLoS One. 2017;12(12):e0188913. doi: 10.1371/journal.pone.0188913. PMID: 29267291
  • Yin J, Nakas CT, Tian L, Reiser B. Confidence intervals for differences between volumes under receiver operating characteristic surfaces (VUS) and generalized Youden indices (GYIs). Statistical Methods in Medical Research. 2017;12:096228021774078–14. doi:10.1177/0962280217740787.
  • von Meyer A, Cadamuro J, Streichert T, Gurr E, Fiedler GM, Leichtle A, Petersmann A, Pick KH, Orth M, Risch L, Sonntag O, Schmitt Y, Wiegel B, Töpfer G, Guder WG. Standard-Arbeitsanleitung zur peripher venösen Blutentnahme für die labormedizinische Diagnostik. LaboratoriumsMedizin 2017; ahead of print, doi:10.1515/labmed-2017-0127
  • Nakas CT, Reiser B. Editorial for the special issue of "Statistical Methods in Medical Research" on "Advanced ROC analysis". Stat Methods Med Res. 2017:962280217742536. doi: 10.1177/0962280217742536. PMID: 29187064
  • Blissenbach B, Nakas CT, Krönke M, Geiser T, Merz TM, Pichler Hefti J. Hypoxia-induced changes in plasma microRNAs correlate with pulmonary artery pressure at high altitude. Am J Physiol Lung Cell Mol Physiol 2017. doi: 10.1152/ajplung.00146.2017
  • Petroulia V, Funke M, Zumstein P, Berezowska S, Ebner L, Geiser T, Torbica N, Heverhagen J, Poellinger A. Increased Expiratory Computed Tomography Density Reveals Possible Abnormalities in Radiologically Preserved Lung Parenchyma in Idiopathic Pulmonary Fibrosis. Investigative Radiology 2017, doi: 10.1097/RLI.0000000000000405
  • Rindlisbacher B, Strebel C, Guler SA, Kollar A, Geiser TK, Fiedler GM, Leichtle AB, Bovet C, Funke M. Exhaled breath condensate as a potential biomarker tool for idiopathic pulmonary fibrosis - a pilot study. J Breath Res. 2017. doi: 10.1088/1752-7163/aa840a. PMID: 28775244
  • Bally L, Bovet C, Nakas CT, Zueger T, Prost JC, Nuoffer JM, Leichtle AB, Fiedler GM, Stettler C. A metabolomics approach to uncover effects of different exercise modalities in type 1 diabetes. Metabolomics 2017, 13: 78. doi:10.1007/s11306-017-1217-8
  • Haider D, Klemenz T, Fiedler GM, Nakas CT, Exadaktylos AK, Leichtle A. In response to the letter to the editor on our manuscript "High sensitive cardiac troponin T: Testing the test" by Dr. Badertscher. Int J Cardiol. 2017;234:127. doi: 10.1016/j.ijcard.2017.01.114. PMID: 28285627
  • Conrad TO, Genzel M, Cvetkovic N, Wulkow N, Leichtle A, Vybiral J, Kutyniok G, Schütte C. Sparse Proteomics Analysis - a compressed sensing-based approach for feature selection and classification of high-dimensional proteomics mass spectrometry data. BMC Bioinformatics. 2017;18(1):160. doi: 10.1186/s12859-017-1565-4. PMID: 28274197
  • Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, Fiedler GM, Wolf S. Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration. Sci Rep. 2017;7:40826. doi: 10.1038/srep40826. PMID: 28094305
  • Pfortmueller CA, Lindner G, Funk GC, Leichtle AB, Fiedler GM, Schwarz C, Exadaktylos AK. Role of D-Dimer testing in venous thromboembolism with concomitant renal insufficiency in critical care. Intensive Care Med. 2017;43(3):470-471. doi: 10.1007/s00134-016-4646-3. PMID: 28011988
  • Haider DG, Klemenz T, Fiedler GM, Nakas CT, Exadaktylos AK, Leichtle AB. High sensitive cardiac troponin T: Testing the test. Int J Cardiol. 2017;228:779-783. doi: 10.1016/j.ijcard.2016.10.043. PMID: 27888755
  • Bally L, Dehais J, Nakas CT, Anthimopoulos M, Laimer M, Rhyner D, Rosenberg G, Zueger T, Diem P, Mougiakakou S, Stettler C. Carbohydrate Estimation Supported by the GoCARB System in Individuals With Type 1 Diabetes: A Randomized Prospective Pilot Study. Diabetes Care. 2017;40(2):e6-e7. doi: 10.2337/dc16-2173. PMID: 27899490

 

2016

  • Gerofotis CD, Ioannou CS, Nakas CT, Papadopoulos NT, The odor of a plant metabolite affects life history traits in dietary restricted adult olive flies. Sci Rep. 2016 Jun 24;6:28540. doi: 10.1038/srep28540, PMID: 27339862
  • Reiser B, Nakas CT, On 'Efficient statistical tests to compare Youden index: accounting for contingency correlation'.Stat Med. 2016 Feb 20;35(4):635-6. doi: 10.1002/sim.6574. PMID: 26776063
  • Lesche D, Geyer R, Lienhard D, Nakas CT, Diserens G, Vermathen P, Leichtle AB, Does centrifugation matter? Centrifugal force and spinning time alter the plasma metabolome. Metabolomics (2016) 12: 159. doi:10.1007/s11306-016-1109-3. PMID:27729833
  • Nakas CT, Schütz N, Werners M, Leichtle AB. Accuracy and Calibration of Computational Approaches for Inpatient Mortality Predictive Modeling. PLoS One. 2016,11(7):e0159046. doi: 10.1371/journal.pone.0159046. PMID: 27414408
  • Sauter TC, Ziegenhorn S, Ahmad SS, Hautz WE, Ricklin ME, Leichtle AB, Fiedler GM, Haider DG, Exadaktylos AK. Age is not associated with intracranial haemorrhage in patients with mild traumatic brain injury and oral anticoagulation. J Negat Results Biomed. 2016, 15(1):12. doi: 10.1186/s12952-016-0055-y. PMID: 27401915
  • Dhayat NA, Ackermann D, Pruijm M, Ponte B, Ehret G, Guessous I, Leichtle AB, Paccaud F, Mohaupt M, Fiedler GM, Devuyst O, Pechère-Bertschi A, Burnier M, Martin PY, Bochud M, Vogt B, Fuster DG. Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function. Kidney Int. 2016, 90(3):648-57. doi: 10.1016/j.kint.2016.04.024. PMID: 27370409
  • Pfortmueller CA, Drexel C, Krähenmann-Müller S, Leichtle AB, Fiedler GM, Lindner G, Exadaktylos AK. S-100 B Concentrations Are a Predictor of Decreased Survival in Patients with Major Trauma, Independently of Head Injury. PLoS One. 2016, 11(3):e0152822. doi: 10.1371/journal.pone.0152822. PMID: 27031106
  • Bally L, Zueger T, Stettler C, Leichtle AB. Computed exercise plasma lactate concentrations: A conversion formula. Practical Laboratory Medicine 2016, 4:11-15, doi:10.1016/j.plabm.2015.11.002.
  • Haider DG, Lindner G, Wolzt M, Leichtle AB, Fiedler GM, Sauter TC, Fuhrmann V, Exadaktylos AK. Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study. J Negat Results Biomed. 2016 Feb 1;15(1):1. doi: 10.1186/s12952-016-0044-1. PMID: 26832747
  • Pichler Hefti J, Leichtle A, Stutz M, Hefti U, Geiser T, Huber AR, Merz TM. Increased endothelial microparticles and oxidative stress at extreme altitude. Eur J Appl Physiol. 2016. [Epub ahead of print], PMID: 26820158

 

 

Chris Nakas is co-author of the trinROC package at the CRAN.

Nenad Torbica is author of the bct package at Github.

Awards

  • 2015 Metabolomics Society Best Paper Award (runner-up)

Grants

SPHN project «e-consent»

This project led by the University Hospital Basel is focusing on simplifying to declare a "general consent" to use health related data of patients for research purposes. As representative of the Inselspital Bern and the Directorate of Teaching and Research, Alexander Leichtle participates in this project funded by the SPHN with 400'000 CHF in total.

SPHN Projekt «L4CHLAB»

This project initiated by the Hôpitaux Universitaires Genève (HUG)aims at harmonizing routine laboratory test denominators using the LOINC nomenclature. As representative of the Inselspital Bern and the University Institute of Clinical Chemistry, Alexander Leichtle participates in this project funded by the SPHN with 200'000 CHF in total.

SPHN project «Swiss BioRef»

This project led by our group is focusing on estabishing a joint lab reference resource across Switzerland. This project funded by the SPHN with 493'350 CHF (plus matching funds).

Link

SNF project «PGXLink»

This project led by our group is focusing on identifying pharmacogenomic, metabolomic, and clinical factors leading to severe infections and complications in patients under immunomodulatory therapy. This project funded by the SNSF with 233'000 CHF.

BCPM project «PGXLink PGM» (Bern Center of Precision Medicine)

This project is the scientific counterpart to the PGXLink infrastructure project, embracing PharmacoGenoMetabolomic (PGM) and bioinformatic analyses. This Project is funded by the BCPM with 197'000 CHF.