Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A Prospective Study in a Population at Risk

Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups

Comparison of normalisation methods for surface-enhanced laser desorption and ionisation (SELDI) time-of-flight (TOF) mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry for biological data analysis is an active field of research, providing an efficient way of high-throughput proteome screening. A popular variant of mass spectrometry is SELDI, which is often used to measure sample populations with the goal of developing (clinical) classifiers. Unfortunately, not only is the data resulting from such measurements quite noisy, variance between replicate measurements of the same sample can be high as well. Normalisation of spectra can greatly reduce the effect of this technical variance and further improve the quality and interpretability of the data. However, it is unclear which normalisation method yields the most informative result.</p> <p>Results</p> <p>In this paper, we describe the first systematic comparison of a wide range of normalisation methods, using two objectives that should be met by a good method. These objectives are minimisation of inter-spectra variance and maximisation of signal with respect to class separation. The former is assessed using an estimation of the coefficient of variation, the latter using the classification performance of three types of classifiers on real-world datasets representing two-class diagnostic problems. To obtain a maximally robust evaluation of a normalisation method, both objectives are evaluated over multiple datasets and multiple configurations of baseline correction and peak detection methods. Results are assessed for statistical significance and visualised to reveal the performance of each normalisation method, in particular with respect to using no normalisation. The normalisation methods described have been implemented in the freely available MASDA R-package.</p> <p>Conclusion</p> <p>In the general case, normalisation of mass spectra is beneficial to the quality of data. The majority of methods we compared performed significantly better than the case in which no normalisation was used. We have shown that normalisation methods that scale spectra by a factor based on the dispersion (e.g., standard deviation) of the data clearly outperform those where a factor based on the central location (e.g., mean) is used. Additional improvements in performance are obtained when these factors are estimated locally, using a sliding window within spectra, instead of globally, over full spectra. The underperforming category of methods using a globally estimated factor based on the central location of the data includes the method used by the majority of SELDI users.</p

Investigation of the adaptation to artificial damping in cerebellar ataxia using the myohaptic technology

We investigated fast pointing and fast reversal single-joint movements performed under artificial damping conditions applied with the myohaptic technology. Healthy subjects were able to scale the intensity of the agonist and antagonist electromyographic (EMG) activities when damping was added during both types of movements. Cerebellar patients were able to scale the magnitude of the agonist and antagonist EMG activities during pointing movements. For reversal movements, patients could scale the intensity of the initial agonist EMG activity but were unable to modulate the intensities of the second set of EMG discharges associated with the return to the initial position. Patients were able to adopt the appropriate motor strategy for the first phase of reversal movements, but they were unable to implement the suitable sequential strategy for the superimposition of motor plans during artificial damping. The myohaptic technology is the first to allow the detection of deficits in the implementation of sequential motor coding under the mechanical condition of artificial damping. © 2009 Springer-Verlag.SCOPUS: cp.pinfo:eu-repo/semantics/publishe

Effects of inertia and wrist oscillations on contralateral neurological postural tremor using the wristalyzer, a new myohaptic device

Upper limb postural tremor consists of mechanical-reflex and central-neurogenic oscillations, superimposed upon a background of irregular fluctuations in muscle force. Muscle spindles play key-roles in the information flow to supra-spinal and spinal generators. Oscillations were delivered using a new generation portable myohaptic device, called "wristalyzer," taking into account the ergonomy of upper limbs and allowing a fine adjustment to each configuration of upper limb segments. The nominal torque of the first generation device is 4 Nm, with a maximal rotation velocity of 300 degrees/s and a range of motion of ±45 degrees. Reliability was assessed in basal condition and during loading conditions. We assessed the effects of the addition of inertia on postural tremor of the finger in a group of 26 neurological patients and the effects of wrist oscillations upon contralateral postural tremor in 6 control subjects and in 7 neurological patients exhibiting a postural tremor. Patients showed two different behaviors in response to inertia and exhibited an increased variability of postural tremor during fast oscillations (13.3 Hz). One patient with overactivity of the olivocerebellar pathways exhibited a drop in the peak frequency of more than 20%. The relative power of the 8-12 Hz subband was significantly higher in controls both in basal condition and during oscillations (p = 0.028 and p = 0.015, respectively). The second generation wristalyzer allows to investigate the effects of mechanical oscillations up to frequency of 50 Hz. This mechatronic device can assess the responsiveness of tremor generators to stimulation of muscle spindles and biomechanical loading. Potential applications are the monitoring of dysmetria under various inertial or damping conditions, the assessment of rigidity in Parkinson's disease and the characterization of voluntary muscle force. © 2008 IEEE.SCOPUS: cp.jinfo:eu-repo/semantics/publishe

A new myohaptic device to assess wrist function in the lab and in the clinic - the wristalyzer

Wristalyzer is a portable robotic device combining haptic technology with electromyographic assessment. It allows to assess wrist motion in physiological and pathological conditions by applying loads and mechanical oscillations, taking into account the ergonomy and the angular positioning of the joints. The wristalyzer works in a free or loaded mode for assessment of metrics of motion and tremor, analyzes the behavior of the wrist joints and the associated muscle activities during delivery of mechanical oscillations, estimates the maximal voluntary contraction, assesses automatically the impedance of the wrist for assessment of rigidity or spasticity. Position, torques and electromyographic activities are analyzed in real time. The device characterizes the effects of damping on voluntary motion. A personal computer implements control loops and user application. This is the first standardized tool to assess wrist motion with high accuracy and reliability using the haptic technology with concomitant investigation of muscle activity. © 2008 Springer-Verlag Berlin Heidelberg.SCOPUS: cp.kinfo:eu-repo/semantics/publishe

Investigation of the Adaptation to Artificial Damping in Cerebellar Ataxia Using the Myohaptic Technology

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