Cerebrospinal fluid (CSF)

Need for RNA biomarkers of neurological disease

Screening RNA biomarkers of neurological disease

Cerebrospinal fluid (CSF) is a clear, colorless liquid that surrounds the brain and spinal cord, providing protection, waste removal, and nourishment to the central nervous system. Since it is in intimate contact with the brain, RNA molecules are secreted from neurons and other brain cell types into CSF. Changes in the RNA profile of CSF inform on altered gene expression in the brain, giving CSF RNA enormous diagnostic and clinical potential.

Why sequence CSF with omiics

Of all cell-free biofluids with ultra-low RNA content, CSF has the lowest, greatly increasing the difficulty of detection by RNA sequencing. Omiics has optimized protocols for detection of both mRNA and miRNA in CSF, allowing detection of a large proportion of genes with good read depth using samples with an RNA content as low as 100 pg (total RNA) or 2 ng (small RNA).

Average logCPM distribution of all genes in the data set plotted. Large proportion of genes detected with good read depth, observed reproducibly across biological replicates

Total RNA

mRNA

lncRNA

circRNA

Small RNAs

miRNA, tRNA fragments (tiRNA), siRNA, piRNA

Case: Differences in the RNA profile of COVID-19 patients

COVID-19 is associated with a range of neurological symptoms including headache, encephalopathy, and stroke, but its actions on the central nervous system remain widely unknown. It is unclear whether these symptoms arise as an indirect consequence of infection or if they are a direct result of an inflammatory response in the CNS.

Characterizing the RNA profile of CSF in COVID-19 patients and identifying neuro-inflammatory markers may provide key insights into the effects of coronavirus infection on the brain.

Challenge:

Identify changes in the RNA profile of CSF in COVID-19 patients compared to healthy and neurological disease controls

Benefits:

+ Assess response to infection at the RNA level

+ Pathway enrichment analysis

Solution:

RNA profiling of CSF revealed 73 linear RNAs upregulated and 28 downregulated in COVID-19 CSF.

Enriched transcripts in COVID-19 CSF were downregulated in COVID-19 cells and tissues — forced RNA secretion as a potential pathomechanism?

Read the full-length publication here

Why sequence CSF with omiics

Case: Differences in the RNA profile of COVID-19 patients

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