SARS-Cov-2 support

[jvwong]

Approach

1. Provide article information
2. Provide expected pathway
3. Provide Factoid manually-created document
4. Issues

1. Article information

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor Hoffmann et al. Cell. 2020 Mar 4. pii: S0092-8674(20)30229-4. [Epub ahead of print]. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA, Drosten C, Pöhlmann S.

2. Factoid manually-created document

3. Issues

• Support for SARS-Cov-2 genes or proteins, in particular, (S)pike protein
• In this case, experimental conditions necessitate only a ACE2 peptidase protein fragment is used
• No 'cleavage' relation for 'TMPRSS2' and 'S'
• No compartments (host, virus)
• Difficult to express macro processes, i.e. 'receptor-mediated endocytosis/entry'

[jvwong]

Similar story for Structure, Function, and Antigenicity of the SARS- CoV-2 Spike Glycoprotein Walls et al., 2020, Cell 180, 1–12

[jvwong]

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Wrapp et al Science 13 Mar 2020: Vol. 367, Issue 6483, pp. 1260-1263

[jvwong]

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Yan et al. Science 27 Mar 2020: Vol. 367, Issue 6485, pp. 1444-1448

• Full length ACE2 protein

[jvwong]

Issues related to Biofactoid support:

• Need to support genes from many viruses
  • Most of what is known relates to other, previously studied coronaviruses (MERS, SARS-Cov)and often other related and un-related viruses, which may or may not extrapolate
• Very idiosyncratic biology related to viruses
  • Self-splicing proteins (NSPs) that arise from open reading frames. This means one gene, many proteins.
  • Translational reading frame slippage
• Detailed post-translational modification ( glycosylation, residues in the spike )
• Email
  • invitations: Need to generate this text distinct from the journal and signup case. Perhaps update the email system to be more generic rather than 'hardcoded' text in the template.

[maxkfranz]

Need to support genes from many viruses

These viruses have distinct taxon IDs, and we decided to only support a predefined set of organisms. To support this, a new root organism must be added, with the strains specified in a way similar to E. coli.

[jvwong]

Need to support genes from many viruses

These viruses have distinct taxon IDs, and we decided to only support a predefined set of organisms. To support this, a new root organism must be added, with the strains specified in a way similar to E. coli.

Taxonomy:

• SARS-COV-2 https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=2697049
• SARS-family of coronaviruses: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=694009&lvl=3&keep=1&srchmode=1&unlock

Genes:

• SARS-COV-2: https://www.ncbi.nlm.nih.gov/gene/?term=txid2697049[Organism:noexp]

Proteins:

• UniProt pre-release: ftp://ftp.uniprot.org/pub/databases/uniprot/pre%5Frelease/

[maxkfranz]

This query gives a good sense of a "spike" or "S" result (but not taking into account any ranking): https://www.ncbi.nlm.nih.gov/gene/?term=spike+glycoprotein

[jvwong]

Sorry I edited above. The SARS-COV-2 genes are there, but most people will want to draw parallels with earlier coronaviruses and related, since well, we know squat. The issue with grounding to 'genes' is that viruses are rather tricky in using one 'gene' to encode a bunch of proteins, hence the uniprot stuff.

[maxkfranz]

The root organism for the virus would be more consistent with how other organisms are specified: 694009 instead of 2697049

[maxkfranz]

Does NCBI have a list of proteins associated with each gene entry in its data? I imagine you could have more specificity in the UI if the gene identifier maps to multiple proteins and the user wants to specify a particular one.

[jvwong]

Let's take this from the start.

1. Below is the SARS-CoV-2 Genome Gordon et al bioRxiv. DNA (black); Gene/mRNAs (orange); proteins (blue, red, green)

   

2. 'Taxonomy'

   • Category of 'Severe acute respiratory syndrome-related coronavirus'
     • SARS-COV-2

3. 'Genes' (i.e. expressed DNA regions) for SARS-COV-2

   • HTML link
   • EUTILS link

4. Proteins associated with the gene/mRNA 'ORF1ab' (orange region in figure)

   • HTML link
   • EUTILS link

Links: NCBI EUTILS 'ELINK'

[maxkfranz]

Let's spec out the details in the grounding service repo in an issue. We need to decide on things like

• what the root organism should be,
• what the display name of the organism family should be,
• what filters may be needed, and
• edge cases (e.g. does "S" work well when the organism is indexed, even though it's only one character).

[jvwong]

In testing driving, I think there may be a strong argument to add-back organism filtering: do show a selector when the search list is available. I found it frustrating to look for an e.g. Drosophila gene and have to zing past a whole bunch of unrelated species, even thought their names are closer.

[jvwong]

Let's spec out the details in the grounding service repo in an issue. We need to decide on things like

* what the root organism should be,

* what the display name of the organism family should be,

* what filters may be needed, and

* edge cases (e.g. does "S" work well when the organism is indexed, even though it's only one character).

I'm moving this issue to that remote....

[jvwong]

Issues related to Biofactoid support:

* Need to support genes from many viruses

  * Most of what is known relates to other, previously studied coronaviruses (MERS, SARS-Cov)and often other related and un-related viruses, which may or may not extrapolate