Tumor Heterogeneity Analysis (THetA) is an algorithm used to estimate tumor purity and clonal/subclonal copy number aberrations simultaneously from high-throughput DNA sequencing data.

References:

• L. Oesper, G. Satas, and B.J. Raphael. Quantifying Tumor Heterogeneity in Whole-Genome and Whole-Exome Sequencing Data. Bioinformatics 2014, 30:3532-3540. Pubmed |  PMC |  Journal

• GitHub
• Home page

• Module Name: theta (see the modules page for more information)
• THetA is a multithreaded application. Please match the number of processes with your allocation.
• Example files in /usr/local/apps/theta/TEST_DATA/example

Allocate an interactive session and run the program. Sample session:

[user@biowulf]$ sinteractive --mem=14g --cpus-per-target=6
salloc.exe: Pending job allocation 46116226
salloc.exe: job 46116226 queued and waiting for resources
salloc.exe: job 46116226 has been allocated resources
salloc.exe: Granted job allocation 46116226
salloc.exe: Waiting for resource configuration
salloc.exe: Nodes cn3144 are ready for job

[user@cn3144 ~]$ module load theta
[user@cn3144 ~]$ cp -r /usr/local/apps/theta/TEST_DATA/example/ .
[user@cn3144 ~]$ RunTHetA example/Example.intervals \
                        --NUM_PROCESSES=$((SLURM_CPUS_PER_TASK - 1)) \
                        --TUMOR_FILE example/TUMOR_SNP.formatted.txt \
                        --NORMAL_FILE example/NORMAL_SNP.formatted.txt
=================================================
Arguments are:
        Query File: example/Example.intervals
        k: 3
        tau: 2
        Output Directory: ./
        Output Prefix: Example
        Num Processes: 4
        Graph extension: .pdf

Valid sample for THetA analysis:
        Ratio Deviation: 0.1
        Min Fraction of Genome Aberrated: 0.05
        Program WILL cluster intervals.
=================================================
Reading in query file...
[...snip...]

[user@cn3144 ~]$ ls -lh
drwxrwx---  2 user group 4.0K May  3  2016 example
drwxrwx---  9 user group 4.0K Aug  2  2017 Example_2_cluster_data
drwxrwx--- 10 user group 4.0K Aug  2  2017 Example_3_cluster_data
-rw-rw----  1 user group  20K Aug  2  2017 Example_assignment.png
-rw-rw----  1 user group 1.7K Aug  2  2017 Example.BEST.results
-rw-rw----  1 user group 155K Aug  2  2017 Example_by_chromosome.png
-rw-rw----  1 user group  24K Aug  2  2017 Example_classifications.png
-rw-rw----  1 user group  18K Aug  2  2017 Example.n2.graph.pdf
-rw-rw----  1 user group 1.7K Aug  2  2017 Example.n2.results
-rw-rw----  1 user group 3.6K Aug  2  2017 Example.n2.withBounds
-rw-rw----  1 user group  19K Aug  2  2017 Example.n3.graph.pdf
-rw-rw----  1 user group 1.8K Aug  2  2017 Example.n3.results
-rw-rw----  1 user group 3.6K Aug  2  2017 Example.n3.withBounds
-rw-rw----  1 user group  251 Aug  2  2017 Example.RunN3.bash

The analysis will create a number of files including some graphs. For example, the following shows one of the models (2 components):

In addition to RunTHetA there are several other tools included in this package

helix$ ls /usr/local/apps/theta/0.7/bin
|-- [  274]  CreateExomeInput
|-- [ 294K]  getAlleleCounts.jar
|-- [  14K]  runBICSeqToTHetA.jar
`-- [  260]  RunTHetA
helix$ java -jar $THETA_JARPATH/runBICSeqToTHetA.jar
Error! Incorrect number of arguments.

Program: BICSeqToTHetA
USAGE (src): java BICSeqToTHetA <INPUT_FILE> [Options]
USAGE (jar): java -jar BICSeqToTHetA <INPUT_FILE> [Options]
<INPUT_FILE> [String]
         A file output by BIC-Seq.
-OUTPUT_PREFIX [STRING]
         Prefix for all output files.
-MIN_LENGTH [Integer]
         The minimum length of intervals to keep.

For a more detailed manual see

/usr/local/apps/theta/<version>/MANUAL.txt

[user@cn3144 ~]$ exit
salloc.exe: Relinquishing job allocation 46116226
[user@biowulf ~]$

Create a batch input file (e.g. THetA.sh), which uses the input file 'THetA.in'. For example:

#! /bin/bash
module load theta || exit 1

alloc_cpus=${SLURM_CPUS_PER_TASK:-4}
nproc=$((alloc_cpus - 1))
RunTHetA example/Example.intervals \
  --NUM_PROCESSES=$nproc \
  --TUMOR_FILE example/TUMOR_SNP.formatted.txt \
  --NORMAL_FILE example/NORMAL_SNP.formatted.txt

Submit this job using the Slurm sbatch command.

sbatch --cpus-per-task=6 --mem=14 theta.sh

Create a swarmfile (e.g. THetA.swarm). For example:

RunTHetA sample1/Example.intervals --NUM_PROCESSES=$((SLURM_CPUS_PER_TASK-1)) \
  --TUMOR_FILE sample1/TUMOR_SNP.formatted.txt --NORMAL_FILE sample2/NORMAL_SNP.formatted.txt
RunTHetA sample2/Example.intervals --NUM_PROCESSES=$((SLURM_CPUS_PER_TASK-1)) \
  --TUMOR_FILE sample2/TUMOR_SNP.formatted.txt --NORMAL_FILE sample2/NORMAL_SNP.formatted.txt

Submit this job using the swarm command.

swarm -f THetA.swarm -g 14 -t 6 --module theta