Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n = 22), moderate (moTBI; n = 14) or mild TBI (mTBI; n = 108) according to Glasgow Coma Scale. The control group (n = 28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n = 23), moTBI (n = 7), mTBI (n = 37) patients and controls (n = 27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC = 0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified ‘TBI metabotype’ in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.
Breast cancer is a major cause of death for women. To improve treatment, current oncology research focuses on discovering and validating new biomarkers for early detection of cancer; so far with limited success. Metabolic profiling of plasma samples and auxiliary lifestyle information was combined by chemometric data fusion. It was possible to create a biocontour, which we define as a complex pattern of relevant biological and phenotypic information. While single markers or known risk factors have close to no predictive value, the developed biocontour provides a forecast which, several years before diagnosis, is on par with how well most current biomarkers can diagnose current cancer. Hence, while e.g. mammography can diagnose current cancer with a sensitivity and specificity of around 75 %, the currently developed biocontour can predict that there is an increased risk that breast cancer will develop in a subject 2–5 years after the sample is taken with sensitivity and specificity well above 80 %. The model was built on data obtained in 1993–1996 and tested on persons sampled a year later in 1997. Metabolic forecasting of cancer by biocontours opens new possibilities for early prediction of individual cancer risk and thus for efficient screening. This may provide new avenues for research into disease mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-015-0793-8) contains supplementary material, which is available to authorized users.
PARAFAC2 is applied in multiple research areas, for example, where data containing shifts are analysed, but it is a challenge to determine the appropriate number of components in the model. In this paper, it is hypothesized that the core consistency diagnostic, which is currently applied in, for example, PARAFAC1 can be used to determine model complexity in PARAFAC2. Theoretically, a PARAFAC1 model is fitted ‘inside’ the PARAFAC2 algorithm, and it should therefore be possible to apply the core consistency diagnostic from PARAFAC1 in PARAFAC2. To support this hypothesis, three different datasets, as well as simulated datasets, have been evaluated by means of PARAFAC2, and the core consistencies have been investigated. There is a general trend that if the core consistency is low, the model is overfitted as in PARAFAC1. Also, core consistency captures the true variation in the data, whereas small peaks are easily overlooked by visual inspection of noisy models. However, for determining the number of components in a PARAFAC2 model, we suggest usage of the core consistency in combination with other model parameters such as residuals, loadings, and split‐half analysis. Copyright © 2013 John Wiley & Sons, Ltd.
The original version of this article unfortunately contained a mistake. In the Materials and methods section the number of samples ready for data analysis is incorrectly given as 301, 295 and 300 for the three groups. The correct numbers are 299, 299 and 289. The incorrect numbers come from an intermediate step in the analysis where some irrelevant standard samples were included. Similar quality of results was obtained on datasets of the size incorrectly given in the paper. The data from the paper can be downloaded from our homepage. http://www.models.life.ku.dk/datasets.The online version of the original article can be found under
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