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README.md updated README Mar 18, 2016

README.md

LS-GKM: A new gkm-SVM software for large-scale datasets

gkm-SVM, a sequence-based method for predicting regulatory DNA elements, is a useful tool for studying gene regulatory mechanisms. In continuous efforts to improve the method, new software, LS-GKM, is introduced. It offers much better scalability and provides further advanced gapped k-mer based kernel functions. As a result, LS-GKM achieves considerably higher accuracy than the original gkm-SVM.

Citation

Please cite the following paper if you use LS-GKM in your research:

  • Ghandi, M.†, Lee, D.†, Mohammad-Noori, M. & Beer, M. A. Enhanced Regulatory Sequence Prediction Using Gapped k-mer Features. PLoS Comput Biol 10, e1003711 (2014). doi:10.1371/journal.pcbi.1003711 † Co-first authors

  • Lee, D. LS-GKM: A new gkm-SVM for large-scale Datasets. Bioinformatics btw142 (2016). doi:10.1093/bioinformatics/btw142

Installation

After downloading and extracting the source codes, type:

$ cd src
$ make 

If successful, You should be able to find the following executables in the current (src) directory:

gkmtrain
gkmpredict

make install will simply copy these two executables to the ../bin direcory

Tutorial

We introduce the users to the basic workflow of LS-GKM. Please refer to help messages for more detailed information of each program. You can access to it by running the programs without any argument/parameter.

Training of LS-GKM

You train a SVM classifier using gkmtrain. It takes three arguments; positive sequence file, negative sequence file, and prefix of output.

Usage: gkmtrain [options] <posfile> <negfile> <outprefix>

 train gkm-SVM using libSVM

Arguments:
 posfile: positive sequence file (FASTA format)
 negfile: negative sequence file (FASTA format)
 outprefix: prefix of output file(s) <outprefix>.model.txt or
            <outprefix>.cvpred.txt

Options:
 -t <0 ~ 5>   set kernel function (default: 4 wgkm)
              NOTE: RBF kernels (3 and 5) work best with -c 10 -g 2
                0 -- gapped-kmer
                1 -- estimated l-mer with full filter
                2 -- estimated l-mer with truncated filter (gkm)
                3 -- gkm + RBF (gkmrbf)
                4 -- gkm + center weighted (wgkm)
                     [weight = max(M, floor(M*exp(-ln(2)*D/H)+1))]
                5 -- gkm + center weighted + RBF (wgkmrbf)
 -l <int>     set word length, 3<=l<=12 (default: 11)
 -k <int>     set number of informative column, k<=l (default: 7)
 -d <int>     set maximum number of mismatches to consider, d<=4 (default: 3)
 -g <float>   set gamma for RBF kernel. -t 3 or 5 only (default: 1.0)
 -M <int>     set the initial value (M) of the exponential decay function
              for wgkm-kernels. max=255, -t 4 or 5 only (default: 50)
 -H <float>   set the half-life parameter (H) that is the distance (D) required
              to fall to half of its initial value in the exponential decay
              function for wgkm-kernels. -t 4 or 5 only (default: 50)
 -c <float>   set the regularization parameter SVM-C (default: 1.0)
 -e <float>   set the precision parameter epsilon (default: 0.001)
 -w <float>   set the parameter SVM-C to w*C for the positive set (default: 1.0)
 -m <float>   set cache memory size in MB (default: 100.0)
              NOTE: Large cache signifcantly reduces runtime. >4Gb is recommended
 -s           if set, use the shrinking heuristics
 -x <int>     set N-fold cross validation mode (default: no cross validation)
 -i <int>     run i-th cross validation only 1<=i<=ncv (default: all)
 -r <int>     set random seed for shuffling in cross validation mode (default: 1)
 -v <0 ~ 4>   set the level of verbosity (default: 2)
                0 -- error msgs only (ERROR)
                1 -- warning msgs (WARN)
                2 -- progress msgs at coarse-grained level (INFO)
                3 -- progress msgs at fine-grained level (DEBUG)
                4 -- progress msgs at finer-grained level (TRACE)
-T <1|4|16>   set the number of threads for parallel calculation, 1, 4, or 16
                 (default: 1)

First try to train a model using simple test files. Type the following command in tests/ directory:

$ ../bin/gkmtrain wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.tr.fa wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.neg.tr.fa test_gkmtrain

It will generate test_gkmtrain.model.txt, which will then be used for scoring of any DNA sequences as described below. This result should be the same as wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.model.txt

You can also perform cross-validation (CV) analysis with -x <N> option. For example, the following command will perform 5-fold CV.

$ ../bin/gkmtrain -x 5 wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.tr.fa wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.neg.tr.fa test_gkmtrain

The result will be stored in test_gkmtrain.cvpred.txt, and this should be the same as wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.cvpred.txt

Please note that it will run SVM training N times, which can take time if training sets are large. In this case, you can perform CV analysis on a specific set by using -i <I> option for parallel runnings. The output will be <outprefix>.cvpred.<I>.txt

The format of the cvpred file is as follows:

[sequenceid] [SVM score] [label] [CV-set]
...

Scoring DNA sequence using gkm-SVM

You use gkmpredict to score any set of sequences.

Usage: gkmpredict [options] <test_seqfile> <model_file> <output_file>

 score test sequences using trained gkm-SVM

Arguments:
 test_seqfile: sequence file for test (fasta format)
 model_file: output of gkmtrain
 output_file: name of output file

Options:
 -v <0|1|2|3|4>  set the level of verbosity (default: 2)
                   0 -- error msgs only (ERROR)
                   1 -- warning msgs (WARN)
                   2 -- progress msgs at coarse-grained level (INFO)
                   3 -- progress msgs at fine-grained level (DEBUG)
                   4 -- progress msgs at finer-grained level (TRACE)
-T <1|4|16>      set the number of threads for parallel calculation, 1, 4, or 16
                 (default: 1)

Here, you will try to score the positive and the negative test sequences. Type:

$ ../bin/gkmpredict wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.test.fa wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.model.txt test_gkmpredict.txt
$ ../bin/gkmpredict wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.neg.test.fa wgEncodeSydhTfbsGm12878Nfe2hStdAlnRep0.model.txt test_gkmpredict.neg.txt

Generating weight files for deltaSVM

You need to generate all possible non-redundant k-mers using the Python script scripts/nrkmers.py. Then, you score them using gkmpredict as described above. The output of lgkmpredict can be directly used by the deltaSVM script deltasvm.pl available from our deltasvm website.

Please email Dongwon Lee (dwlee AT jhu DOT edu) if you have any questions.

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