A novel parametric approach to mine gene regulatory relationship from microarray datasets

<p>Abstract</p> <p>Background</p> <p>Microarray has been widely used to measure the gene expression level on the genome scale in the current decade. Many algorithms have been developed to reconstruct gene regulatory networks based on microarray data. Unfortunately, most of these models and algorithms focus on global properties of the expression of genes in regulatory networks. And few of them are able to offer intuitive parameters. We wonder whether some simple but basic characteristics of microarray datasets can be found to identify the potential gene regulatory relationship.</p> <p>Results</p> <p>Based on expression correlation, expression level variation and vectors derived from microarray expression levels, we first introduced several novel parameters to measure the characters of regulating gene pairs. Subsequently, we used the naïve Bayesian network to integrate these features as well as the functional co-annotation between transcription factors and their target genes. Then, based on the character of time-delay from the expression profile, we were able to predict the existence and direction of the regulatory relationship respectively.</p> <p>Conclusions</p> <p>Several novel parameters have been proposed and integrated to identify the regulatory relationship. This new model is proved to be of higher efficacy than that of individual features. It is believed that our parametric approach can serve as a fast approach for regulatory relationship mining.</p

Regular Patterns for Proteome-Wide Distribution of Protein Abundance across Species

A proteome of the bio-entity, including cell, tissue, organ, and organism, consists of proteins of diverse abundance. The principle that determines the abundance of different proteins in a proteome is of fundamental significance for an understanding of the building blocks of the bio-entity. Here, we report three regular patterns in the proteome-wide distribution of protein abundance across species such as human, mouse, fly, worm, yeast, and bacteria: in most cases, protein abundance is positively correlated with the protein's origination time or sequence conservation during evolution; it is negatively correlated with the protein's domain number and positively correlated with domain coverage in protein structure, and the correlations became stronger during the course of evolution; protein abundance can be further stratified by the function of the protein, whereby proteins that act on material conversion and transportation (mass category) are more abundant than those that act on information modulation (information category). Thus, protein abundance is intrinsically related to the protein's inherent characters of evolution, structure, and function

Analysis of rainstorm-induced slide-debris flows on natural terrain of Lantau Island, Hong Kong

Lantau Island, the largest outlying island of the territory of Hong Kong, experienced a severe rainstorm on 4-5 November 1993, which induced >800 slope failures on natural terrain there. Detailed field investigations were carried out to study the failure modes, in relation with various influencing factors. It was found that the occurrence of slide-debris flows has a close relationship with bedrock geology, slope gradient, vegetation cover and micro landform. The failure modes of slide-debris flows may be classified into translational slides and rotational slides, and the former are predominant. Analysis of the hydrological response of colluvial slopes during the rainstorm indicated that the majority of the failures were caused by the development of a perched water table in the thin surface layer of colluvium of volcanic origin due to infiltration during the heavy rain. Undisturbed soil samples from south Lantau have been subjected to anisotropically consolidated undrained compression tests at comparatively low stress levels. Constant deviatoric stress path tests (CQD) simulating the stress path in the field at in situ stress levels have been performed to investigate soil behavior. The CQD test results indicate that the material of slopes at undisturbed state is brought to dilation because of the increase in pore water pressure caused by infiltration of rain water. For a translational slide, the displacement, resulting from dilation, may destroy cohesion along the failure surface and locally within the interior of the slide. The surplus water during the intense rainstorm was able to equilibrate the reduction in pore pressure caused by dilation, and the dilation and displacement may be further increased. The strain-softening after significant strains triggered debris flow mobilization. However, for a rotational slide, the increase in pore water pressure caused by surplus water infiltration during the intense rainstorm could not equilibrate the reduction in pore pressure caused by dilation, much or even all of the sliding block could not mobilize into a debris flow. | Lantau Island experienced a severe rainstorm on November 4-5, 1993, inducing >800 slope failures in natural terrain. Detailed field investigations were carried out to study the failure modes in relation to various influencing factors. The occurrence of slide-debris flows has a close relationship with bedrock geology, slope gradient, vegetation cover and micro-landform. The analysis of the hydrological response of colluvial slopes during the rainstorm indicated that the majority of the failures were caused by the development of a perched water table in the thin surface layer of the colluvium of volcanic origin due to infiltration during heavy rain.link_to_subscribed_fulltex

ER-associated ubiquitin ligase HRD1 programs liver metabolism by targeting multiple metabolic enzymes

The HMG-CoA reductase degradation protein 1 (HRD1) has been identified as a key enzyme for endoplasmic reticulum-associated degradation of misfolded proteins, but its organ-specific physiological functions remain largely undefined. Here we show that mice with HRD1 deletion specifically in the liver display increased energy expenditure and are resistant to HFD-induced obesity and liver steatosis and insulin resistance. Proteomic analysis identifies a HRD1 interactome, a large portion of which includes metabolic regulators. Loss of HRD1 results in elevated ENTPD5, CPT2, RMND1, and HSD17B4 protein levels and a consequent hyperactivation of both AMPK and AKT pathways. Genome-wide mRNA sequencing revealed that HRD1-deficiency reprograms liver metabolic gene expression profiles, including suppressing genes involved in glycogenesis and lipogenesis and upregulating genes involved in glycolysis and fatty acid oxidation. We propose HRD1 as a liver metabolic regulator and a potential drug target for obesity, fatty liver disease, and insulin resistance associated with the metabolic syndrome.Special Funds for Major State Basic Research of China [2014CBA02001]; National Institutes of Health (NIH) [AI079056, AI108634, AR006634]; NIH [DK090313, 5P01AG049665]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]