Sep

29

Upcoming RNA-Seq Webinar

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Using IPA® to analyze Illumina RNA-Seq data reveals abundance-specific biological signatures in Alzheimer’s Disease

Date: Monday, October 10, 2011     Time: 9:00 a.m. (PST)
Speaker: Darryl Gietzen, Ph.D., Field Application Scientist, Ingenuity Systems

IPA was used to interpret Alzheimer’s disease biology by comparing Illumina RNA-Seq data from Alzheimer’s disease (AD) and normal brain samples. This analysis revealed very specific biological changes in certain classes of transcript expression, demonstrating how the unique benefits of RNA-Seq can help characterize disease changes.

In this webinar, we will discuss how:

  • IPA maximizes RNA-Seq data analysis
  • Grouping and analyzing all significantly changed genes in RNA-Seq data can provide pathway level information
  • The sensitivity and accuracy of RNA-Seq enables pathway analysis on a subset of genes to elucidate more subtle biological changes

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Feb

8

Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer’s disease.

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Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer’s disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD.

This study provides, for the first time, transcriptomic analysis for distinct regions of the Alzheimer’s disease (AD) brain using RNA-Seq next-generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. Gene expression levels, splicing isoforms and alternative transcript start sites were quantified.

Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron’s cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. These results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration.

Twine NA, Janitz K, Wilkins MR, Janitz M. (2011) Whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by Alzheimer’s disease. PLoS One 6(1), e16266. [article]

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Dec

29

RNA-Seq to deliver a quantum leap forward in understanding Alzheimer’s disease

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The prevalence of Alzheimer’s disease (AD) is increasing rapidly in the Western world and is poised to have a significant economic and societal impact. Current treatments do not alter the underlying disease processes meaning new treatments are required if this imminent epidemic is to be averted. The clinical manifestations of AD are secondary to a substantial loss of cortical neurons.

Effective neuroprotective strategies will require the discovery of both preclinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. While the biomarkers and pathogenic mechanisms may overlap, it is likely that new approaches are required to identify novel elements of the disease.

Transcriptomic analyses, that assume no a priori etiological hypotheses, promise much in elucidating the pathogenesis of complex diseases like AD. RNA-Seq is not only highly suited to investigations of the genomically complex human brain tissue but it can potentially overcome technical issues inherent to case-control comparisons of postmortem brain tissue in neurodegenerative diseases. Moreover, RNA-Seq goes beyond the detection of transcripts that correspond to an existing genomic sequence. With this technique, the exact location of transcription boundaries can be identified with single base resolution. These features make RNA-Seq particularly useful for studying complex transcriptomes, such as those found in the human brain.

Sutherland GT, Janitz M, Kril JJ. (2010) RNA-Seq and the pathogenesis of Alzheimer’s disease.  Journal of Neurochemistry [Epub ahead of print]. [article]

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