Dahlin, L. B. | bioRxiv Science

bioRxiv2024

Inferring the composition of the blood plasma proteome by a human proteome distribution atlas

The plasma proteome is maintained by the influx and efflux of proteins from surrounding organs and cells. To quantify the extent different organs and cells contribute to the plasma proteome composition, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in human plasma in health and disease. First, we constructed an extensive human proteome atlas from 18 vascularized organs and the most abundant cell types in blood. Second, the atlas was interfaced with previous RNA/protein atlases to objectively define proteome wide protein-organ associations to enable both the inference of origin and the reproducible quantification of organ-specific proteins in plasma. We demonstrate that the resource can determine disease-specific quantitative changes of organ-enriched protein panels in three separate patient cohorts with infection, pancreatitis, and myocardial injury. The strategy can be extended to other diseases to advance our understanding of the processes contributing to plasma proteome dynamics.

systems biology↗

bioRxiv2019

Vibrotactile perception in the sole of the foot in people with normal glucose tolerance and type 2 diabetes

AimTo evaluate vibrotactile perception thresholds in people with normal glucose tolerance (NGT) and type 2 diabetes (T2DM) in relation to other sensory tests. MethodsNerve function was evaluated in 36 and 42 participants with NGT and T2DM, respectively [mean age 70.0 (1.2) years; males n=40, females n=38]. The mean duration of T2DM was 12.3 (7.3) years. Vibration perception thresholds were measured at four frequencies (8, 16, 32 and 125 Hz) bilaterally on the sole of the foot at first and fifth metatarsal heads using Multifrequency vibrametry and compared to vibration perception thresholds using Biothesiometer (128 Hz) bilaterally (medial malleolus and distal dorsal bony surface of great toes), touch sensation with Semmes-Weinstein monofilament bilaterally (10 g) at three sites on the sole of foot (distal great toe and 1st and 5th metatarsal heads), electrophysiology (amplitude and conduction velocity of sural nerve; right side) and thermal sensory testing (i.e. small diameter nerve fibers; method of limits using Thermotest(R)). ResultsVibration perception and temperature thresholds in the foot and sural nerve function were different between the NGT and T2DM categories. Measuring vibration perception thresholds at lower frequencies with Multifrequency vibrametry, compared to Biothesiometer, both provided similar correlations to the amplitude of the sural nerve. Temperature thresholds did also correlate with vibration perception thresholds and with sural nerve function. Only 4/42 participants with T2DM showed pathology by monofilament test, none with NGT. ConclusionsVibration perception thresholds have a fair correlation to amplitude of the sural nerve, even when measured at a non-tactile surface. Thus in the present study, measuring vibration perception threshold at a tactile surface does not seem to provide any clear advantage over the traditional way of measuring vibration perception on the medial malleolus. In people with T2DM, both large and small diameter nerve fibers seem to be affected.

neuroscience↗