Study: Functional study

Model: HEK293 cell lines

Variant: VWF NM_000552.5: c.7664C>G, p.(Pro2555Arg), described as GOF mutation

rare missense variant, MAF = 0.00007

RefSNP_ID:rs915754316

Not reported in ClinVar

Cells lines were transfected and expressed one of the following: wtVWF, p.Pro2555Arg, both variants, or a negative control variant p.Asp2509Glu

Main result:

p.Pro2555Arg is the first VWF GOF variant that increases platelet aggregate size (AS), which is shear-dependent and independent of fibrinogen (fb). May provide a novel risk factor for thromboembolic disease.

Additional results:

Variant does not affect the binding affinity of the C4 domain for BPIIb/IIIa

VWF stem region mutations can enhance VWF's prothrombotic properties

C4 domain of VWF may be a novel antithrombotic drug target.

Variant: VWF NM_000552.5: c.7682T>A p.(Phe2561Tyr)

Suggested GOF mechanism

Located in exon 45 of VWF (C4 domain)

Present in gnomAD, suggested as likely benign/benign Found in exome and genome samples (Allele count is 69570, allele freq = 4.32e-2, homozygote count= 1725)

Note that the assessment here is primarily in white individuals

Also supplementary: system landscape, deployment.

Internal to some business unit. External systems may still be part of the same enterprise.

Could this be represented in XMI?

I wonder what it would be like to model this in Fibery.

Except if e.g. a component is used in different containers.

C4 understands something, but eschews knowledge of e.g. the exact same component being used within different containers.

You also deploy instances of them in specific environments.

Is it possible to model the intermediary, such that it shows upon a deployment diagram, but leave it out of this diagram?

Also enterprise to show external/internal?

Would be nice to track elements across those boundaries. I.e. this system in C4 is that business unit in ArchiMate. Kind of like context propagation in distibuted tracing.

No: include the entire system in a single model. Diagrams should be focused views.

How do I do that in the DSL?

These teams, however, also want models. They see inside of those software systems. This should be just another view. On one model that contains elements for everything in the system.

The OpenTelemetry Collector is a single binary but can be deployed in different roles in order to scale horizontally

How about internal architecture?