PTM Stoichiometry

[pcruzparri]

Creating a mzLib method to calculate the stoichiometry (or site-occupancy) of PTMs using the intensity of each quantified peak. The current inputs are the protein database(s) file(.xml) paths and the AllQuantifiedPeaks.tsv file path. The output, occupancyDict, is currently a dictionary of nested dictionaries with the following structure:

{{string PROTEIN1, {{int MAA1, {{string MODNAME1, double INTENSITY}, 
                                {string MODNAME2, double INTENSITY},
                                ...,
                                {string "Total", double INTENSITY}}} 
                    {int MAA2, {...}}, 
                   ...}},
 {string PROTEIN2, {...}},
 ...}

where PROTEINX is the protein accession, MAAX is the modified amino acid at protein position X, and MODNAME1 is the full label of the modification. For each MAAX, there is a "Total" key (instead of a modification name) that holds the total intensity of that amino acid measured in the quantified peaks file, including modified and unmodified peptides with that specific residue.

The general approach is to first get all of the modification intensities and record those in occupancyDict while storing in proteinSeqRangesSeen a dictionary with protein accession keys and values stored as a list of (STARTINDEX, ENDINDEX, INTENSITY) tuples. This helps keep track of the index ranges seen for each protein. Once we have parsed all of the mods, for every amino acid falling into any of those ranges, we increase its "Total" intensity by that amount.

From our discussion, I've added below some of the items I'd like to get some opinions about. Imade them a task list primarily for me to keep track of what I've figured out.

• Where should this code live in mzLib. The most reasonable suggestions so far are in FlashLFQResults and Readers/QuantificationResults.
• To interface this nicely with MetaMorpheus, what should the inputs be? My goal now is to look into how/where this will be integrated into MM, but any suggestions on places to look to figure this out are appreciated.
• I have some ideas on making the code more efficient/succinct, especially foreseeing a lot more information about the peaks being readily available in MM (like the exact protein index for a peptide/peak). Any new ideas are welcomed.

Thanks in advance!

[Alexander-Sol]

In situations like this, you can use "var aaWithModList" instead of specifying the actual class

[nbollis]

I think readers/Quant... is the best place for it. That way it can be used to find occupancy of the results from another software should that be desired.

In order to optimize your inputs and outputs of the function, you should break your test method into two. One test method with reads in all the data you need. Another method (not a test method) that gets called to calculate the occupancy. This will help you to better understand what is needed for the method, and for use to help make recommendations

[pcruzparri]

Requesting a second round of reviews! The second to last commit contains a little more in detail most changes. Currently pending work is to create a small enough subset of the raw data to create a test similar to the TestFlashLFQoutputRealData() test. More rigorous testing can be done with some of the identifications in the vignette data, since some base sequences have enough variations in fullSequence mods and positions to have better case coverage.

I'd be happy to hear about 1) code optimization, 2) currently written tests, and 3) clarifications on code commenting. In a conversation, Nic suggested using objects for my main ptm calculation code rather than the 5-level deep dictionary, thoughts on that would be useful as well. Ofc, anything else is useful. TIA!

[codecov]

Codecov Report

Attention: Patch coverage is 92.05500% with 104 lines in your changes missing coverage. Please review.

Project coverage is 76.51%. Comparing base (983c3b0) to head (b146768).
Report is 1 commits behind head on master.

Files with missing lines	Patch %	Lines
...zLib/Transcriptomics/Digestion/OligoWithSetMods.cs	87.78%	20 Missing and 7 partials ⚠️
mzLib/UsefulProteomicsDatabases/ProteinDbWriter.cs	88.23%	9 Missing and 3 partials ⚠️
mzLib/Transcriptomics/NucleicAcid.cs	92.08%	6 Missing and 5 partials ⚠️
mzLib/MzLibUtil/PositionFrequencyAnalysis.cs	89.79%	7 Missing and 3 partials ⚠️
...ProteomicsDatabases/Transcriptomics/RnaDbLoader.cs	93.71%	3 Missing and 7 partials ⚠️
mzLib/UsefulProteomicsDatabases/ProteinXmlEntry.cs	79.54%	6 Missing and 3 partials ⚠️
mzLib/MzLibUtil/ClassExtensions.cs	79.48%	6 Missing and 2 partials ⚠️
mzLib/Transcriptomics/ClassExtensions.cs	93.84%	1 Missing and 3 partials ⚠️
...zLib/Transcriptomics/Digestion/NucleolyticOligo.cs	96.39%	1 Missing and 3 partials ⚠️
mzLib/FlashLFQ/Peptide.cs	57.14%	2 Missing and 1 partial ⚠️
... and 3 more

Additional details and impacted files

@@            Coverage Diff             @@
##           master     #797      +/-   ##
==========================================
+ Coverage   75.52%   76.51%   +0.99%     
==========================================
  Files         202      212      +10     
  Lines       30945    32091    +1146     
  Branches     3129     3304     +175     
==========================================
+ Hits        23371    24556    +1185     
+ Misses       7040     6969      -71     
- Partials      534      566      +32     

Files with missing lines	Coverage Δ
mzLib/Chemistry/ClassExtensions.cs	100.00% <100.00%> (ø)
mzLib/FlashLFQ/FlashLFQResults.cs	92.02% <100.00%> (+0.17%)	⬆️
mzLib/FlashLFQ/FlashLfqEngine.cs	87.62% <100.00%> (+0.01%)	⬆️
mzLib/MzLibUtil/MzLibException.cs	100.00% <100.00%> (ø)
.../Fragmentation/Oligo/DissociationTypeCollection.cs	100.00% <100.00%> (+100.00%)	⬆️
...ragmentation/Oligo/TerminusSpecificProductTypes.cs	100.00% <100.00%> (ø)
mzLib/Omics/IBioPolymerWithSetMods.cs	95.23% <ø> (ø)
mzLib/Omics/SpectrumMatch/SpectrumMatchFromTsv.cs	97.05% <100.00%> (-0.29%)	⬇️
...ib/Transcriptomics/Digestion/RnaDigestionParams.cs	100.00% <100.00%> (ø)
mzLib/Transcriptomics/Digestion/Rnase.cs	100.00% <100.00%> (ø)
... and 15 more

... and 4 files with indirect coverage changes