jbloomlab / seqneut-pipeline

Pipeline for analyzing sequencing-based neutralization assays
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reasonable suggestions for `fixslope` range for example / docs #36

Closed jbloom closed 5 months ago

jbloom commented 6 months ago

In #35, it was implemented to enable fixslope to constrain the slope to a range (see #32).

However, more analysis of real data is needed to see if the suggested range in the example ([0.8, 5]) is actually reasonable for serum.

Check this on real data and adjust accordingly.

anloes commented 5 months ago

For fixslope, I initially tested [0.8-6] as the starting range, as for the DRIVE cohort data, where this parameter was not constrained, this range appeared to capture the majority of well-fit curves (~65%).

I also tested [0.8,10] with the most recent data, and I do have a large number of curves fitting with the max slope within the range permitted (either 6 or 10, respectively), but I think that may be partially a result how the error in the most recent plates is impacting the shape of these curves, i.e. we have many curves with no points in the slope or only a single point in the slope. The resulting midpoint titers are quite similar, as would be expected. I would expect that the larger this max slope is the more variability we might observe between slopes fit for samples with sharp curves like this, so a smaller range is likely preferable. Though, I will repeat this test once we have additional plates to confirm that these parameters are reasonable.

ckikawa commented 5 months ago

Similar to @anloes, I have also been constraining fixslope to a fairly loose range of [0.8, 10]. I agree that the difference between midpoints called with [0.8, 10] versus [0.8, 5] is likely to be minimal, but for now, I will probably continue to use this wider range until I have more data. I'm currently only testing with 9 individuals.

In the future, since there's no real biological reason (?) to point to for allowing such steep slopes, I agree that reducing the upper bound is probably better.