Biology subjects

Kochan, N.

Publications and source records attributed to Kochan, N..

5 recordsLinked to original sources

bioRxiv2020

Age-related changes of Peak width Skeletonized Mean Diffusivity (PSMD) across the adult life span: a multi-cohort study

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and meta-analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing DTI metrics. For each individual MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40 and 50, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process.

neuroscience↗

bioRxiv2019

A new local covariance matrix estimation for the classification of gene expression profiles in RNA-Seq data

Background and ObjectiveRecent developments in the next-generation sequencing (NGS) based on RNA-sequencing (RNA-Seq) allow researchers to measure the expression levels of thousands of genes for multiple samples simultaneously. In order to analyze these kind of data sets, many classification models have been proposed in the literature. Most of the existing classifiers assume that genes are independent; however, this is not a realistic approach for real RNA-Seq classification problems. For this reason, some other classification methods, which incorporates the dependence structure between genes into a model, are proposed. qtQDA proposed by Kochan et al. [1] is one of those classifiers, which estimates covariance matrix by Maximum Likelihood Estimator.\n\nMethodsIn this study, we use a another approach based on local dependence function to estimate the covariance matrix to be used in the qtQDA classification model. We investigate the impact of different covariance estimates on RNA-Seq data classification.\n\nResultsThe performances of qtQDA classifier based on two different covariance matrix estimates are compared over two real RNA-Seq data sets, in terms of classification error rates. The results show that using local dependence function approach yields a better estimate of covariance matrix and increases the performance of qtQDA classifier.\n\nConclusionIncorporating the true/accurate covariance matrix into the classification model is an important and crucial step particularly for cancer prediction. The local covariance matrix estimate allows researchers to classify cancer patients based on gene expression profiles more accurately. R code for local dependence function is available at https://github.com/Necla/LocalDependence.

bioinformatics↗

bioRxiv2019

qtQDA: quantile transformed quadratic discriminant analysis for high-dimensional RNA-seq data

Classification on the basis of gene expression data derived from RNA-seq promises to become an important part of modern medicine. We propose a new classification method based on a model where the data is marginally negative binomial but dependent, thereby incorporating the dependence known to be present between measurements from different genes. The method, called qtQDA, works by first performing a quantile transformation (qt) then applying Gaussian Quadratic Discriminant Analysis (QDA) using regularized covariance matrix estimates. We show that qtQDA has excellent performance when applied to real data sets and has advantages over some existing approaches. An R package implementing the method is also available.

bioinformatics↗

bioRxiv2018

Differentiation of Alzheimer’s disease based on local and global parameters in personalized Virtual Brain models

Alzheimers disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, \"The Virtual Brain (TVB)\", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioral spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

neuroscience↗

bioRxiv2017

The independent influences of age and education on functional brain networks and cognition in healthy older adults

Healthy ageing is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during ageing in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identify three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively-normal elders. The first mode (p=0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode (p=0.012), characterised by the involvement of key hub-regions. A third mode (p=0.041) captures weak, residual brain-behaviour relations. Our findings suggest that circuits supporting lower-level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks - suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with ageing. This has important implications in understanding the contribution of education to cognitive reserve during healthy ageing.

neuroscience↗