A Strategy For Identifying Putative Causes Of Gene Expression Variation In Human Cancer

There is often a need to predict the impact of alterations in one variable on another variable. This is especially the case in cancer research, where much effort has been made to carry out large-scale gene expression screening by microarray techniques. However, the causes of this variability from one cancer to another and from one gene to another often remain unknown. In this study we present a systematic procedure for finding genes whose expression is altered by an intrinsic or extrinsic explanatory phenomenon. The procedure has three stages: preprocessing, data integration and statistical analysis. We tested and verified the utility of this approach in a study, where expression and copy number of 13,824 genes were determined in 14 breast cancer samples. The expression of 270 genes could be explained by the variability of gene copy number. These genes may represent an important set of primary, genetically "damaged" genes that drive cancer progression

Computing the output distribution and selection probabilities of a stack filter from the DNF of its positive Boolean function

Many nonlinear filters used in practise are stack filters. An algorithm is presented which calculates the output distribution of an arbitrary stack filter S from the disjunctive normal form (DNF) of its underlying positive Boolean function. The so called selection probabilities can be computed along the way.Comment: This is the version published in Journal of Mathematical Imaging and Vision, online first, 1 august 201

Vaccines, Repurposed Drugs and Alternative Biomedicines for the Management and Prevention of COVID-19

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Robust regression for periodicity detection in non-uniformly sampled time-course gene expression data

<p>Abstract</p> <p>Background</p> <p>In practice many biological time series measurements, including gene microarrays, are conducted at time points that seem to be interesting in the biologist's opinion and not necessarily at fixed time intervals. In many circumstances we are interested in finding targets that are expressed periodically. To tackle the problems of uneven sampling and unknown type of noise in periodicity detection, we propose to use robust regression.</p> <p>Methods</p> <p>The aim of this paper is to develop a general framework for robust periodicity detection and review and rank different approaches by means of simulations. We also show the results for some real measurement data.</p> <p>Results</p> <p>The simulation results clearly show that when the sampling of time series gets more and more uneven, the methods that assume even sampling become unusable. We find that M-estimation provides a good compromise between robustness and computational efficiency.</p> <p>Conclusion</p> <p>Since uneven sampling occurs often in biological measurements, the robust methods developed in this paper are expected to have many uses. The regression based formulation of the periodicity detection problem easily adapts to non-uniform sampling. Using robust regression helps to reject inconsistently behaving data points.</p> <p>Availability</p> <p>The implementations are currently available for Matlab and will be made available for the users of R as well. More information can be found in the web-supplement <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p

Protein-protein interaction and coarse grained simulation study of glioblastoma multiforme reveals novel pathways of Gpr17

Studies of receptor mediated signaling networks in neuronal cells provide a unique opportunity to uncover the basis of many diseases. Receptor signaling cascades proceed from the cell surface, where extra cellular factors interact with their specific receptors e.g. G-Protein Coupled Receptors (GPR). Recent studies have shown that the activation or suppression of GPR 17 in diseased neuronal cells has potential impact in altering the tumor con ditions. We identified many hundred times expressions of GPR 17 in Glioblastoma Multiforme (GBM) from the RNA -Seq data. We also observed many other genes having similar expression patterns with GPR 17, indicating possible connections of this receptor with diverse gene products. We performed a coarse-grained simulation of ∼500 proteins inside a cytoplasm like a box with solvent water molecules. The summarized protein interaction networks resulted from a coarse grained simulation and large scale protein-protein docking reveals novel molecular connections and pathways

Delayed stochastic model of transcription at the single nucleotide level

We present a delayed stochastic model of transcription at the single nucleotide level. The model accounts for the promoter open complex formation and includes alternative pathways to elongation, namely pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination. We confront the dynamics of this detailed model with a single-step multi-delayed stochastic model and with measurements of expression of a repressed gene at the single molecule level. At low expression rates both models match the experiments but, at higher rates the two models differ significantly, with consequences to cell-to-cell phenotypic variability. The alternative pathway reactions, due to, for example, causing polymerases to collide more often on the template, are the cause for the difference in dynamical behaviors. Next, we confront the model with measurements of the transcriptional dynamics at the single RNA level of an induced gene and show that RNA production, besides its bursting dynamics, also exhibits pulses (2 or more RNAs produced in intervals smaller than the smallest interval between initiations). The distribution of occurrences and amplitudes of pulses match the experimental measurements. This pulsing and the noise at the elongation stage are shown to play a role in the dynamics of a genetic switch.Peer reviewe