Allow compositing a Molecular Species with a DNA backbone to show binding?

[jakebeal]

John Sexton observes that a molecular species in contact with a DNA backbone is often used to show binding into a complex in a diagram. We should consider whether SBOL Visual can be extended to allow this:

John Sexton wrote:

In Section 6.3, the standard dictates that molecular species glyphs MUST NOT contact a nucleic acid backbone (page 14, line 3). I think this is unnecessarily restrictive; DNA binding domains of proteins often interact with DNA molecules but are still classified as molecular species. In the Tabor lab in particular, bacterial two-component systems are often illustrated as dimerized protein domains binding a DNA backbone (see [1], [2], [3], [4], [5]). These diagrams are currently not compliant with SBOL Visual 2.0 given the specification that molecular species MUST NOT touch a DNA backbone. I understand that edits to this document should not be substantive, but was this requirement included in a vote? I don't see it in SEP V008.

[jakebeal]

@JS3xton I'd like to try to resolve this: can you please draw some specific use cases diagrams for us to consider? I think that looking at a few diagrams will give a clear path forward.

[JS3xton]

Here are a few examples I could scrounge together quickly. They all seem to fall into the category of illustrating a protein, proteins, or protein-RNA complexes binding DNA.

Transcriptional regulators:

• Fig 5.22, panel 4 from Ptashne's A Genetic Switch, 3rd Edition, 2004 on phage lambda regulation:
• Fig 2 from Schleif, FEMS Microbiol Rev, 2010 on arabinose operon regulation:
• Other systems for which I don't have primary literature diagrams at the moment: lac operon, trp operon.

CRISPR and derivatives:

• Fig 5A from Jinek et al, Science, 2012 introducing CRISPR:
• Fig 1B and Fig 3B from Qi et al, Cell, 2013 introducing CRISPR interference (CRISPRi):
• Fig 1A from Nielsen & Voigt, Mol Syst Biol, 2014 on CRISPRi logic circuits:

Two-component system (TCS) biosensors:

• Fig 1a from Levskaya et al, Nature, 2005 on engineering light sensors in E. coli:
• Fig 1D from Tabor et al, Cell, 2009 describing a bacterial edge detector:
• Fig 1a and Fig 1d from Schmidl et al, ACS Synth Biol, 2014:
• Very similar diagrams can also be found in:
  • Olson et al, Nature Methods, 2014
  • Ramakrishnan & Tabor, ACS Synth Biol, 2016
  • Daeffler et al, Mol Syst Biol, 2017
  • Olson, Tzouanas, Tabor, Mol Syst Biol, 2017
  • Ong, Olson, Tabor, ACS Synth Biol, 2018
  • Landry et al, Nature Comm, 2018

[jakebeal]

So it looks like we would have no ambiguity there, at least, since the Macromolecule glyph is very different from all of the Sequence Feature glyphs.

Places where I do see potential ambiguity:

• Small Molecule vs. Origin of Replication - do small molecules ever bind directly?
• SBGN Unspecified Molecule vs. Origin of Replication - Unspecified is NOT RECOMMENDED anyway.
• SBGN Unspecified nucleic acid vs. SBGN Unspecified Sequence Feature - Unspecified is NOT RECOMMENDED anyway.

Regarding contact: if it's an RNA binding (e.g., siRNA), would that make an acceptable diagram? How would you draw that to look nice?

[jakebeal]

I have created an SEP to address this issue: #74