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README.md

TMAP - torrent mapping alignment program

General Notes

TMAP is a fast and accurate alignment software for short and long nucleotide sequences produced by next-generation sequencing technologies.

  • The latest TMAP is unsupported. To use a supported version, please see the TMAP version associated with a Torrent Suite release below.

  • Get the latest source code:

    git clone git://github.com/iontorrent/TMAP.git
     cd TMAP
     git submodule init
     git submodule update
     
  • To download a specific version, please get the latest source code, and then checkout the specific version using the tag listed below:

    git checkout -b tag "tag name below"

    For example:

    git checkout -b 3.0.1 tmap.3.0.1
    git submodule update
    Below is the list of tags associated with a specific Torrent Suite release:

    Torrent Suite 3.0:tmap.3.0.1
    Torrent Suite 2.2tmap.0.3.7
    Torrent Suite 2.0.1tmap.0.2.3
    Torrent Suite 2.0tmap.0.2.3
    Torrent Suite 1.5.1tmap.0.1.3
    Torrent Suite 1.5tmap.0.1.3
    Torrent Suite 1.4.1tmap.0.0.28
    Torrent Suite 1.4tmap.0.0.25
    Torrent Suite 1.3tmap.0.0.19
    Torrent Suite 1.2tmap.0.0.9
  • See the latest manual: http://github.com/iontorrent/TMAP/blob/master/doc/tmap-book.pdf

Pre-requisites

  1. Compiler (required): The compiler and system must support SSE2 instructions.

To Install

  1. Compile TMAP:
sh autogen.sh && ./configure && make
  1. Install
make install

Optional Installs

TCMalloc (optional)

TMAP will run approximately 15% faster using the tcmalloc memory allocation implementation. To use tcmalloc, install the Google performance tools: http://code.google.com/p/google-perftools

If you have previously compiled TMAP, execute the following command:

make distclean && sh autogen.sh && ./configure && make clean && make

After installation, execute the following command:

sh autogen.sh && ./configure && make clean && make

The performance improve should occur when using multiple-threads.

Developer Notes

There are a number of areas for potential improvement within TMAP for those that are interested; they will be mentioned here. A great way to find places where the code can be improved is to use Google's performance tools: http://code.google.com/p/google-perftools This includes a heap checker, heap profiler, and cpu profiler. Examining performance on large genomes (hg19) is recommended.

Smith Waterman extensions

Currently, each hit is examined with Smith Waterman (score only), which re-considers the portion of the read that matched during seeding. We need only re-examine the portion of the read that is not matched during seeding. This could be tracked during seeding for the Smith Waterman step, though the merging of hits from each algorithm could be complicated by this step. Nonetheless, this would improve the run time of the program, especially for high-quality data and/or longer reads (>200bp).

Smith Waterman vectorization

The vectorized (SSE2) Smith Waterman implemented supports an combination of start and end soft-clipping. To support any type of soft-clipping, some performance trade-offs needed to be made. In particular, 16-bit integers are stored in the 128-bit integers, giving only 8 bytes/values per 128-bit integer. This could be improved to 16 bytes/values per 128-bit integer by using 8-bit integers. This would require better overflow handling. Also, handling negative infinity for the Smith Waterman initialization would be difficult. Nonetheless, this could significantly improve the performance of the most expensive portion of the program.

Best two-stage mapping

There is no current recommendation for the best settings for two-stage mapping, which could significantly decrease the running time. A good project would be to optimize these settings.

Mapping quality calibration

The mapping quality is sufficiently calibrated, but can always be improved, especially for longer reads. This is a major area for improvement.

Better support for paired ends/mate pairs

There is minimal support for paired ends/mate pairs, which relies on knowing a prior the parameters for the insert size distribution. The insert size could be trained on a subset of the given input data.

Speeding up lookups in the FM-index/BWT.

Further implementation improvements or parameter tuning could be made to make the lookups in the FM-index/BWT faster. This includes the occurrence interval, the suffix array interval, and the k-mer occurence hash. Caching these results may also make sense when examining the same sub-strings across multiple algorithms. Speed improvements have already been made to BWA and could be relevant here: http://github.com/RoelKluin/bwa

Dynamic split read mapping

It is important to detect Structural Variation (SV), as well as finding splice junctions for RNA-seq. Support for returning more than one alignment, where these alignments do not significantly overlap in terms of which bases they consume in the query, could be included. For example, a 400bp read could span a SV breakpiont, with the first 100bp on one side of the breakpoint and the second 300bp on the other. Currently (with full soft-clipping options turned on), we may produce two alignments for the two parts of the query. Nonetheless, the "choice" algorithm will choose the one with the best alignment score (typically the 300bp one), and so only one alignment will be present in the SAM file. A better strategy would be to search for pairs (triples, etc.) of alignments that do not significantly overlap in the query (i.e. consume the same query bases). This would directly find SVs as well as other types of variant requiring split read mapping.

Representative repetitive hits

If a seeding algorithm finds a large occurence interval that it will save, it could save one of the occurrences (random) as a representative hit for the repetitive interval. This representative hit could be aligned with Smith-Waterman and its alignment score could be compared to the other hits. If its score is better, than the read could be flagged as repetitive and "unmapped". The algorithm would need to be careful that the repetitive hit is not contained within the returned non-repeititve hits, as to cause many reads to be unmapped.