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Comparison of Differentially Expressed Genes in Brain and Spinal Cord Regions Involved in sALS

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Ishav Desai, Carlos Ovalle, Joshua Prupes, Vinit Shah, Evan Shrestha, Michael Truong, Megan Chan�

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Background of Neurons

  • Upper motor neurons in brain cortex send signal to lower motor neurons in spinal cord
  • Dendrites pick up the signals
    • Signal travels towards axon terminal
  • Impaired motor neurons
    • Spasticity
    • Apoptosis

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Background of sALS

ALS is a neurodegenerative disorder that deteriorates motor neurons in the brain and spinal cord. Over 90% of ALS cases are sporadic ALS while the other 10% are familial ALS. Unlike familial ALS, sporadic ALS occurs at irregular intervals and randomly within the population.

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Symptoms of ALS

  • Muscle cramping
  • Impaired motor function
  • Muscle atrophy
  • Lack of interneural cell communication

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Overview of our project

  • Identify differentially expressed genes in each brain region and spinal cord between sALS and healthy subjects
  • Determine the effect these genes have on the human body

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Materials: Datasets

Spinal Neuron Dataset

Brain Regions Dataset

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Methodology

  • Format the data
  • Filter the data
  • Create preliminary PCA plot
  • Run hypothesis tests
  • Analysis of data
    • Data visualization
    • ENRICHR/PANTHER

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Filtering and Normalization

  • Filter out c9 samples from brain regions dataset
  • Retrieve gene lengths from BioMart
  • Compute log2(RPKM)

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Results: Preliminary PCA Plots

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Results: MA Plots

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Results: Heatmaps

Frontal Cortex

Cerebellum

Spinal Regions

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Results: Venn Diagram

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Results: ENRICHR Pathways

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Results: G-Protein Pathway

  • Membrane-associated genes
  • Acts as primary and secondary messenger
  • Important genes such as RGS8, RGS3

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Discussion of our project

  • Limitations
    • Normalizing across datasets
    • BioMart data for brain regions dataset
    • Duplicates in datasets
  • Implications
    • Spine and Brain Datasets in ALS have common dysregulated genes
    • Dysregulated genes linked to ALS function
    • Possible use for earlier diagnosis/alternative treatment

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Thanks!

Any questions ?

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