DynaMet: A Fully Automated Pipeline for Dynamic LC–MS Data

Dynamic isotope labeling data provides crucial information about the operation of metabolic pathways and are commonly generated via liquid chromatography–mass spectrometry (LC–MS). Metabolome-wide analysis is challenging as it requires grouping of metabolite features over different samples. We developed DynaMet for fully automated investigations of isotope labeling experiments from LC-high-resolution MS raw data. DynaMet enables untargeted extraction of metabolite labeling profiles and provides integrated tools for expressive data visualization. To validate DynaMet we first used time course labeling data of the model strain <i>Bacillus methanolicus</i> from ¹³C methanol resulting in complex spectra in multicarbon compounds. Analysis of two biological replicates revealed high robustness and reproducibility of the pipeline. In total, DynaMet extracted 386 features showing dynamic labeling within 10 min. Of these features, 357 could be fitted by implemented kinetic models. Feature identification against KEGG database resulted in 215 matches covering multiple pathways of core metabolism and major biosynthetic routes. Moreover, we performed time course labeling experiment with <i>Escherichia coli</i> on uniformly labeled ¹³C glucose resulting in a comparable number of detected features with labeling profiles of high quality. The distinct labeling patterns of common central metabolites generated from both model bacteria can readily be explained by one versus multicarbon compound metabolism. DynaMet is freely available as an extension package for Python based eMZed2, an open source framework built for rapid development of LC–MS data analysis workflows

Neurophysiological and MRI data 4

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Neurophysiological and MRI data 3

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Neurophysiological and MRI data 1

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure

<div><p>Background</p><p>In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance.</p><p>Methods</p><p>20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance.</p><p>Results</p><p>Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance.</p><p>Conclusions</p><p>Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.</p></div

Neuropsychological assessment.

<p>Neuropsychological assessment.</p

Neurophysiological and MRI data 2

The files contain neurophysiological and MRI (T2 weighted MRI, Diffusion Tensor Imaging) data from 20 patients with primary biliary cholangitis and 20 controls

Computerized test battery of attention performance.

<p>20 patients with PBC and 20 age- and sex-matched controls underwent a computerized test battery of attention performance (TAP) in order of the figure appearance. No differences of reaction time were observed between both groups within all subtests (Wilcoxon matched pairs test). Alertness I without and with warning signal (WS) (A), divided attention auditive/visual (B), 30 minutes vigilance test first half/second half (C), alertness II without and with warning signal (WS) (D). PBC, primary biliary cholangitis.</p

Voxel-based morphometry.

<p>Voxel-based morphometry.</p

Patient characteristics.

<p>Patient characteristics.</p