2.0 version

MAAG

• Implement shifts in event probabilities.
  • In Clonotypes.
  • In MAAGBuilder.
• Replace generation probability computing with forward-algo-like procedure.
• Add MarkovChain with errors.
  • Tests
• Implement errors in MAAGBuilder.
  • V.
  • D.
  • J.
• Implement errors in MAAGForward-backward.
  • VJ (waiting for 100K test)
  • VDJ
• Implement errors in alignments.
• Fix replacement of MAAG event probe in MAAGBuilder.
• Add move assignment operator to MAAG.
• With which value initialise error probability?

PAM

• Implement a PAM + inference algorithm with errors in alignments.
  • VJ
  • VDJ
• Fix segfault
  "There are four common mistakes that lead to segmentation faults: dereferencing NULL, dereferencing an uninitialized pointer, dereferencing a pointer that has been freed (or deleted, in C++) or that has gone out of scope (in the case of arrays declared in functions), and writing off the end of an array.
  A fifth way of causing a segfault is a recursive function that uses all of the stack space. On some systems, this will cause a "stack overflow" report, and on others, it will merely appear as another type of segmentation fault. "

IO

• Fix Python converter (V / D / J alignments column instead of starts/ends columns)
• Fix writer
• Refactor parser.
• Refactor parser with the new aligner with virtual functions instead of templates.
• Implement a separate class for align all genes on clonotypes sequences. Pass it as a object to Parser if you (user) want to.
  • Implement SW local aligner for Variable genes.
  • Implement SW local aligner for Joining genes.
• Add translation subroutine.
• Add aligner parameters for alignment - thresholds for length / score, etc.

2.1 version

MAAG

• Add MarkovChain to MAAG (for amino acids).
  • VJ
  • VDJ
• Implement MAAGaa
  • VJ
  • VDJ
• Implement amino acid sequence MAAG builder.
  • Tests.

IO

• Implement amino acid aligner.
  • VJ
    • Tests.
  • VDJ
    • Tests.

2.2 version

PAM

• Data diversity measure.
• Implement and test new secret EM algorithm.
  • Save #iter for each parameter, not globally.

2.3 version

Optimisations

• Add parallelisation.
  • Parallel MAAG building.
  • Parallel marginal probs updates in EM.
    http://www.futurechips.org/tips-for-power-coders/writing-optimizing-parallel-programs-complete.html
• Optimise MAAG updating in the builder.
• Replace objects in MAAGBuilder with pointers.
• Do not reallocate ProbMMC in MAAGForwardBackward at each step. Just resize and clear it so reserved space won't change.
• Compute full prob while building MAAGs and store them in MAAGs.

2.4 version

Docs

• Add support for high precision numbers or decide to work only with long doubles.
• Write API documentation using Doxygen.
• Write general / usage documentation using MkDocs.
• Publish all documentation on GitHub pages.

2.5 version

IO

• MAAG serialization.
  • Binary representation.
    • Tests.
  • Reading.
    • Tests.
  • Writing.
    • Tests.
• ??? Memory mapped MAAG repertoire in case of very large files (align -> save to disk -> read from the memory mapped file).

Far Future

MAAG

• Add checks for zero or error gene segments and other events in MAAG builder.

AAPAG

• Implement AAPAG (Amino Acid Pattern Assembly Graph).
• Implement fast generation of neighbour amino acid sequences.

Optimisations

• Play with SIMD https://github.com/p12tic/libsimdpp
  • markov chains, probs in forward-backward
  • computing of full probabilities
• Rewrite all using templates - in this case code will be without unnecessary "ifs". Basic scripts (compute, inference and generate) for each possible recombination.
• Do return value optimisation everywhere when possible.
• Check if lazy evaluation can be added anywhere.
• Decide to refactor or not MarkovChain in MAAGBuilder.
• Branching (if - statements) optimisations.
  • Try to always build event indices MMC, just do not include it to the resulting MAAG.
  • Move if (full_build) from the cycles to their own out cycles with only one cycle in MAAGBuilder.
  • ?: instead of if-else in MAAGBuilder deletions and insertions.
• Check speed in ClonotypeBuilder in returning void vs returning ClonotypeBuilder& procedures.
• Use fixed-size matrices in some cases like VJ deletions because all VJ gene segments sequences are pretty similar in size. (???)
• Rewrite ModelParameterVector with plain arrays.
• Optimise sequence class (currently std::string, need speed and memory improvements using bit vectors).
• Compilation options which removes all verbosing for speed.

Refactoring

• Replace all raw pointer with std::unique_ptr.
• Add Google Test instead of my test.
• Shared ptr for VDJRecombinationGenes.

Other

• Add error rate as a argument to the script.
• Models as gzipped folders.
• Add speed benchmarks.
  • https://bruun.co/2012/02/07/easy-cpp-benchmarking
  • https://github.com/DigitalInBlue/Celero
• Compute estimation of MAAG matrices memory and compare it to the graph representation (pointers occupy memory too!). In the mean matrix representation should be more space efficient.
• Installation instructions for GMP and GCC: https://github.com/davidsd/sdpb/blob/master/Readme.md#mac-os-x-installation
• Add progress bars.
  http://stackoverflow.com/questions/14539867/how-to-display-a-progress-indicator-in-pure-c-c-cout-printf
  https://gist.github.com/cmckni3/6420109
• ?? Design an R package for the cloneset analysis using the generation probabilities with interface to call the Ymir tool.
• ?? Add a bunch of Python scripts for the easy integration of Ymir to other software tools and scripts.
• Add binary (very comfortable! but not-human readable) format for models (parameters and sequences).
  • Add Python script for converting between text <-> binary representations.
  • Always save both representations.
• Add an easy way to create models from existing models with different parameters.
• ?? Docker container for Ymir?
• Add the "Algorithm" field to model JSON files.
• Add pybind11 and https://github.com/tbenthompson/cppimport