Curated sequence example
Make a tau assay distinguish 3R from 4R
A tau program aiming to change the balance between 3R and 4R needs a readout that separates them. BioTwin’s curated MAPT catalogue makes the distinction concrete: compare the 2N3R and 2N4R entries while holding their N-terminal inserts constant.
- 410 aa2N3R tau
Exon 10 is excluded.
- 441 aa2N4R tau
Exon 10 is included.
- 31 aaThe distinction to measure
An additional microtubule-binding repeat.
- What goes in and comes back · The input is a named pair of MAPT protein products and their exon annotations. The comparison identifies the included or excluded sequence, giving the program a precise protein identity to carry into an assay or structural analysis.
- How it changes the experiment · If the question is whether an intervention changes the 3R/4R balance, retain total tau as an abundance readout and add an assay that resolves exon 10 inclusion or the corresponding protein products. A change in the total alone cannot identify which product changed.
- What the comparison establishes · Transcript resources such as Ensembl already represent this distinction. BioTwin makes the protein identity explicit in the intervention question and its follow-up inputs, so an assay or structural calculation can address the intended product.
Move from the gene label to the therapeutic job
Resources such as Ensembl already represent transcripts, exons and translated protein sequences. BioTwin’s curated assessment uses isoform context to challenge an intervention hypothesis: are the relevant products interchangeable, or could suppressing one have a different consequence from suppressing another?
Put the distinction into the assay
Compare the relevant sequence, expression and functional annotations, then identify the assay that can separate the products in the intended setting. A gene-level readout may be adequate for one question and conceal the distinction that matters for another.
A targeted assessment, with coverage stated
Current work supports curated isoform comparisons. It does not establish exhaustive isoform coverage or measured isoform selectivity. Expression and function in the target tissue are evidence to obtain, rather than properties to infer from a transcript label.
Carry the right protein product into the next calculation
An interface or modification-state analysis could change when its input sequence changes. An RNA-directed strategy raises a related question about transcript specificity. Each requires its own compatible inputs and functional evidence.
- Protein interfaces · Investigate the arrangement for the relevant protein product. Protein interfaces
- Modification context · Consider the sequence and modification state together. Modification context
