TCR generation probabilities

[RachelKarchin]

[dltamayo]

TCR generation probability: the process of VDJ recombination results in certain CDR3 sequences having a higher probability of occurring. This probability can be computed.

Implement module to calculate TCR generation probability for each CDR3 sequence in sample. @yuvalel will advise what software package to use.

Related: https://www.pnas.org/doi/pdf/10.1073/pnas.1409572111

[yuvalel]

For TCR generation probability we should use the OLGA package - https://github.com/statbiophys/OLGA
It computes fast the generation probability for clones, based on previous recombination models.
It can use different clone definitions, we should just use the CDR3 amino acid chain as the clone.

[dltamayo]

Input to Olga: vector of CDR3 aa chains for clones in one sample
Output: vector of probabilities for clones of that sample

[RachelKarchin]

Next steps:
histogram of generation probabilties for a single sample

Identify a baseline repertoire.
Emerson dataset ! (use all individuals)
prepare histograms of each Emerson individual

is the test sample "healthy"?

ks test?

[favorov]

There is a very reliable measure of distribution-to-distribution distance, OT (Optimal Transport) aka Wassershtein distance. Having all the pairwise Emerson-to-Emarson sample distances calculated, we can position any new sample relative to Emerson samples looking at its sample-to-Emerson samples distances.
The OT distance for 1-D distribution has some simple form, kind of $\int_0^1 |F_1(x)-F_2(x)| dx$, where F are cumulative probabilities.

[dimalvovs]

@KevinMLanderos do you know where the Emerson dataset to test the idea ?

[dltamayo]

@KevinMLanderos do you know where the Emerson dataset to test the idea ?

@dimalvovs I think this is the dataset. n=666 in original cohort and n=120 in independent validation cohort:
https://clients.adaptivebiotech.com/pub/emerson-2017-natgen