Mass spectrometry tools and metabolite-specific databases for molecular identification in metabolomics.

The chemical identification of mass spectrometric signals in metabolomic applications is important to provide conversion of analytical data to biological knowledge about metabolic pathways. The complexity of electrospray mass spectrometric data acquired from a range of samples (serum, urine, yeast intracellular extracts, yeast metabolic footprints, placental tissue metabolic footprints) has been investigated and has defined the frequency of different ion types routinely detected. Although some ion types were expected (protonated and deprotonated peaks, isotope peaks, multiply charged peaks) others were not expected (sodium formate adduct ions). In parallel, the Manchester Metabolomics Database (MMD) has been constructed with data from genome scale metabolic reconstructions, HMDB, KEGG, Lipid Maps, BioCyc and DrugBank to provide knowledge on 42,687 endogenous and exogenous metabolite species. The combination of accurate mass data for a large collection of metabolites, theoretical isotope abundance data and knowledge of the different ion types detected provided a greater number of electrospray mass spectrometric signals which were putatively identified and with greater confidence in the samples studied. To provide definitive identification metabolite-specific mass spectral libraries for UPLC-MS and GC-MS have been constructed for 1,065 commercially available authentic standards. The MMD data are available at http://dbkgroup.org/MMD/.

A flexible measure of contextual similarity for biomedical terms.

We present a measure of contextual similarity for biomedical terms. The contextual features need to be explored, because newly coined terms are not explicitly described and efficiently stored in biomedical ontologies and their inner features (e.g. morphologic or orthographic) do not always provide sufficient information about the properties of the underlying concepts. The context of each term can be represented as a sequence of syntactic elements annotated with biomedical information retrieved from an ontology. The sequences of contextual elements may be matched approximately by edit distance defined as the minimal cost incurred by the changes (including insertion, deletion and replacement) needed to transform one sequence into the other. Our approach augments the traditional concept of edit distance by elements of linguistic and biomedical knowledge, which together provide flexible selection of contextual features and their comparison.

Serum amyloid A protein in patients with acute myocardial infarction.

The concentrations of four acute phase proteins were measured in sera of 40 patients with acute myocardial infarction (AMI) to evaluate their behaviour from day-to-day and to find out if they can serve for early prediction of postinfarction complications and mortality rate. Peak levels of serum amyloid A protein (SAA) were increased up to 5000-fold above the normal value and those of C-reactive protein (CRP) about 100-fold, 3 days after AMI. alpha 1-antichymotrypsin (ACT) and alpha 1-acid glycoprotein (AGP) peak levels were increased up to eightfold above their normal values. Patients who developed postinfarction complications had significantly higher SAA values on admission than those without complications (mean values of 379 and 45 mg/L, respectively; P < 0.0001). Using a level of 100 mg/L on admission as a reference value gave a reasonable sensitivity and predictive value for complications (73%) and a very good sensitivity (80%) for early prediction of fatal outcome. Patients with SAA values above this limit had double the risk of complications and four times the risk of a fatal outcome. The correlation with CRP values was lower than it was with SAA values (P = 0.028) using a level of 15 mg/L on admission as reference value gave low sensitivity (55%) and predictive value (60%) for complications as well as low sensitivity for early prediction of fatal outcome (60%). The present study did not allow prediction of complications or mortality based on ACT or AGP values.

The differential diagnostic capacity of serum amyloid A protein between infectious and non-infectious febrile episodes of neutropenic patients with acute leukemia.

We studied the behavior of four major acute phase proteins (SAA, CRP, ACT and AGP) in pyrexial occurrences of 16 neutropenic patients with acute leukemia. Altogether 37 febrile episodes were recorded; 27 were infectious in origin (microbiologically documented infection and clinically documented infection, MDI/CDI group) and 10 were pyrexias of unknown origin (PUO group). In the MDI/CDI group the mean value for the highest individual SAA concentration was 282 +/- 161 mg/l and in the PUO group 95 +/- 79 mg/l. The corresponding mean values were 4.0 mg/l (range 0.2-5.5 mg/l) in 10 control patients with 1 year remission and 0.8 mg/l (range < 0.1-1.2 mg/l) in 30 healthy adults. The peak value of SAA rose above 100 mg/l in 85% of our MDI/CDI pyrexias and in 40% of PUO. More reliable results were obtained when the difference between the value on the day when pyrexia occurred and the previous day was calculated. In that case, the difference was above 75 mg/l in 23 of 27 (85%) MDI/CDI pyrexias and in none of 10 (0%) PUO. In the MDI/CDI group the mean difference was 204 +/- 137 mg/l while it was only 26 +/- 19 mg/l in the PUO group. The statistical significance was very high (p < 0.0001). The CRP monitoring was very inferior to SAA while ACT and AGP monitorings were unsatisfactory.