4 ms·

They found out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' in Covid patients than normally and they conclude that

by zby 6y ago

They found out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' in Covid patients than normally and they conclude that that must have resulted in too much bradykinine. Hmm - that strikes me as kind of roundabout - why they couldn't just measure bradykinine levels directly? Is that too hard? "Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension."

brandmeyer 6y ago
> They analyzed the human genome and SARS-CoV-2 genome to find out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' by the Covid-19 virus than normally and they observed known biochemical pathways that are hypothesized to lead to too much bradykinine. FTFY. They didn't measure patients. They modeled genomic interactions to make some predictions about biochemical effects on patients. Then they noted that some of those predicted effects correlate with symptoms of Covid patients. They went further and shotgunned a list of treatments which are known to affect the same biochemical processes. The farther along the path of inference, the weaker the conclusions get, but it sounds like a promising arrow for research to me. > why they couldn't just measure bradykinine levels directly? Is that too hard? Don't need nearly as much permission or human resources to run computer simulations on offline data as you do to take measurements of patients in the hospital.
08-15 6y ago
> why they couldn't just measure bradykinine levels directly? Is that too hard? It is. To measure gene expression, you isolate total mRNA and sequence it. This tells you the expression of all genes simultaneously. The protocol is fairly standard, cheap, and quick. That doesn't tell you anything about bradykinine, though, because there is no mRNA that codes for it. In contrast, no such protocol exists for proteins. Sequencing a single protein is comparatively difficult, and no high throughput device exists that sequences lots of proteins, let alone quantifies their abundance. The traditional lab methods like PAGE gels are slow and labor intensive.
- robwwilliams 6y ago
  This comment on quantitative protein assays is only partly correct. It is definitely harder than quantitative assays of messenger RNA (aka “gene expression” and not as comprehensive. But there are now hundreds of quantitative proteomic studies that survey 5000 or more proteins in single samples (and their peptide fragments). Search PubMed for the author “Aebersold R”.
  - AnthonBerg 6y ago
    Thank you for a great comment!, the crisp context is a good gateway for further reading. Could I ask you for any hints about where/how to learn more? And/or if there's a way to follow your work online?

by zby 6y ago

brandmeyer 6y ago

> They analyzed the human genome and SARS-CoV-2 genome to find out that some genes related to ACE in comparison to genes related to ACE2 are more 'expressed' by the Covid-19 virus than normally and they observed known biochemical pathways that are hypothesized to lead to too much bradykinine. FTFY. They didn't measure patients. They modeled genomic interactions to make some predictions about biochemical effects on patients. Then they noted that some of those predicted effects correlate with symptoms of Covid patients. They went further and shotgunned a list of treatments which are known to affect the same biochemical processes. The farther along the path of inference, the weaker the conclusions get, but it sounds like a promising arrow for research to me. > why they couldn't just measure bradykinine levels directly? Is that too hard? Don't need nearly as much permission or human resources to run computer simulations on offline data as you do to take measurements of patients in the hospital.

08-15 6y ago

> why they couldn't just measure bradykinine levels directly? Is that too hard? It is. To measure gene expression, you isolate total mRNA and sequence it. This tells you the expression of all genes simultaneously. The protocol is fairly standard, cheap, and quick. That doesn't tell you anything about bradykinine, though, because there is no mRNA that codes for it. In contrast, no such protocol exists for proteins. Sequencing a single protein is comparatively difficult, and no high throughput device exists that sequences lots of proteins, let alone quantifies their abundance. The traditional lab methods like PAGE gels are slow and labor intensive.

robwwilliams 6y ago
This comment on quantitative protein assays is only partly correct. It is definitely harder than quantitative assays of messenger RNA (aka “gene expression” and not as comprehensive. But there are now hundreds of quantitative proteomic studies that survey 5000 or more proteins in single samples (and their peptide fragments). Search PubMed for the author “Aebersold R”.
- AnthonBerg 6y ago
  Thank you for a great comment!, the crisp context is a good gateway for further reading. Could I ask you for any hints about where/how to learn more? And/or if there's a way to follow your work online?