2017.12.29 31

OK, now that tSNE did not reveal anything much (at least what I can interpret anyway), I will just try to do the validation study for the DESeq2 results. I will do this by cross-checking the genes that were marked to be differentially- expressed with literature. The limitation is that even if a gene is not found in literature to be associated with any stage of the disease progression, it does not necessarily mean that the gene has nothing to do with the disease at all. For all we know, maybe we discovered something new (unlikely, but possible).

One quick way of checking the functions of the differentially-expressed (DE) genes is just to go to UniProt and check the gene symbols for their functions. With the H->S and S->N progressions, I did not filter the genes to only ones present in the liver as there were so few anyway.

• H->S:
  • All 5 genes are up-regulated.
  • Two genes code for chemokines and the other 3 relate to structural function (chitin degradation, keratin formation and regulator of collagen matrix formation).
  • Opinion: This kind of makes sense as steatosis (and the subsequent progressions) are marked by the formation of fibrils in the liver yet at the same time the body does not like it so chemokines are released triggering inflammatory response cascade.
• S->N:
  • All 5 genes are down-regulated.
  • Genes involved in cell-cell adhesion, force generation for respiratory cilia, protein transport, IL1R ligand 1 and (what I think is most probably related) a major acute phase protein (perhaps this signifies the inflammatory process?).
• N->C: oh boy
  • These have been filtered to only ones that are expressed in the liver.
  • In total there are 12: 2 down-regulated and 10 up-regulated.
  • The down-regulated genes are involved in protein-protein interaction and in terms of its GO functions, negatively regulate apoptotic process, cell differentiation & transcription and positively regulate cell proliferation.
  • Opinion: These sounds pretty much like what cancerous tissue would do to promote its own survival.
  • The up-regulated genes vary much more, from aiding the metabolism of exogenous agent (e.g. drugs) to transcription factors and an epigenetic factor. There is also one DE gene that was said to be involved in detection of pathogens by the peripheral immune surveillance in the liver.
• All the opinions <-- require further literature review.