The Human Leukocyte Antigen (HLA) genes play a major role in adaptive immune response and are used to differentiale self cells from non self cells. HLA genes are hyper variable with nearly evrery locus containing over a dozen alleles. This variation plays an important role in autoimmune diesease and organ transplantation. HLA typing by serological methods is time consuming and expensive. We present a new computational method to infer per-locus HLA types using shared segments Identical By Descent (IBD), inferred from genotype data.
The program has been developed in Itsik Pe'er's Lab of Computational Genetics at Columbia University. It is built in Java 1.5 and tested in the Red Hat Linux environment; the source is distributed here in a tar.gz package under the GPL license.
Installation and Usage
Ant and log4j are required for installation. Download Ant from here. Download log4j from here. After installing ant, extract the archive using tar xvzf hla_ibd.tar.gz from the command line. Enter the extracted directory and build the jar using ant jar. This creates the hlaibd.jar file. This file and the downloaded log4j jar file should be included in the classpath for running the application.
Invocation
Use the command java -cp iplab.hla.HLAIBDMain <inputs> for invocation
The following inputs should be passed
- GERMLINE matches file
- HLA types file. File containing the HLA type information. Sample file here
- Chromosome span start
- Chromosome span end
This region will be used for determining the IBD matches which
will be part of the graph. Testing was done using the
chromosomal region spanning 100kb upstream to 100kb downstream
of the HLA gene being analyzed.
- Output file name
Output
Sample output
| INDIVIDUAL | | RESOLVED-STATUS | | TYPES |
|---|
| 884M02 | | 1 | | 101 301 |
| 884F02 | | 2 | | 201 101 301 1501 |
| 884C04M | | 3 | | 2501 |
The resolved status is defined as follows
- Individual assigned both the HLA types
- Ambiguous resolution: First type in the list is assigned as one of the HLA types. The second HLA type is predicted to be any one of the listed files.
- Individual could be homozygous in the listed type.
Logging
The default logging information is set to info. The logs will written both to the console and the log file HLA.log. The log4j options can be changed by editting log4j.properties in the install directory.
For any question or comments please contact mn2370@columbia.edu or itsik@cs.columbia.edu