An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver

<p>Abstract</p> <p>Background</p> <p>Many groups, including our own, have proposed the use of DNA methylation profiles as biomarkers for various disease states. While much research has been done identifying DNA methylation signatures in cancer vs. normal etc., we still lack sufficient knowledge of the role that differential methylation plays during normal cellular differentiation and tissue specification. We also need thorough, genome level studies to determine the meaning of methylation of individual CpG dinucleotides in terms of gene expression.</p> <p>Results</p> <p>In this study, we have used (insert statistical method here) to compile unique DNA methylation signatures from normal human heart, lung, and kidney using the Illumina Infinium 27 K methylation arraysand compared those to gene expression by RNA sequencing. We have identified unique signatures of global DNA methylation for human heart, kidney and liver, and showed that DNA methylation data can be used to correctly classify various tissues. It indicates that DNA methylation reflects tissue specificity and may play an important role in tissue differentiation. The integrative analysis of methylation and RNA-Seq data showed that gene methylation and its transcriptional levels were comprehensively correlated. The location of methylation markers in terms of distance to transcription start site and CpG island showed no effects on the regulation of gene expression by DNA methylation in normal tissues.</p> <p>Conclusions</p> <p>This study showed that an integrative analysis of methylation array and RNA-Seq data can be utilized to discover the global regulation of gene expression by DNA methylation and suggests that DNA methylation plays an important role in normal tissue differentiation via modulation of gene expression.</p

From genes to networks: in systematic points of view

We present a report of the BIOCOMP'10 - The 2010 International Conference on Bioinformatics & Computational Biology and other related work in the area of systems biology

Preliminary Analysis of β-Methylamino-L-Alanine Interactions With Cu/Zn Superoxide Dismutase in Amyotrophic Lateral Sclerosis Zebrafish Models

Amyotrophic Lateral Sclerosis (ALS) is a terminal neurodegenerative disease with symptoms including limb-onset muscle wasting, difficulties swallowing and breathing, leading to death. Sporadic ALS occurs in 90% of patients, while 10% of cases are familial (FALS). Twenty percent of FALS cases are a result of mutation in the copper-zinc superoxide dismutase (SOD1) gene, leading to the activation of the mitochondrial apoptosis pathway. Meanwhile, a prominent cause of sporadic ALS is exposure to neurotoxins, such as β-methylamino-L-alanine (BMAA). BMAA has been suggested to induce selective motor neuron death, which is observed in ALS patients. While research has been done to how BMAA may impacts organisms on the cellular level, not much has been performed on the genetic or epigenetic level. This research investigates how BMAA and mutations in the SOD1 gene affect the regulation of well- known neurological genes. Within the year, zebrafish from four different genotypes were subjected to three different BMAA concentrations, and spinal samples from these fish were collected. RNA was extracted from these and cDNA was produced from the resulting RNA. RNA concentrations varied significantly in concentration and purity, while cDNA concentrations were more pure and higher in concentration. The spinal samples also displayed that fish exposed to 2.5 μg/L of BMAA had the lowest levels of actin transcripts, reflected in previous work that these fish would have the shortest motor neuron axons. These samples can now be used to perform transcriptome analysis to detect the regulation of neurological genes depending on BMAA concentration and SOD1 mutation