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<HTML>
<CENTER><A HREF = "main.html">Return to Steve Plimpton's home page</A>
</CENTER>
<HR>
<H3>Parallel Genehunter
</H3>
<P>This page describes work done primarily by Gavin Conant, then at the
University of New Mexico, with a code from the MIT Whitehead Institute
called Genehunter. This work was a collaboration between the UNM
Biology Dept, Sandia National Labs, and Pam Fain's group at the
University of Colorado. Gavin's participation was funded by DOE thru
its computational science graduate fellowship (CSGF) program; Sandia's
efforts were funded by DOE's Office of Biological and Environmental
Research (OBER).
</P>
<P>Genehunter is software package for locating human genetic diseases
using linkage analysis. Linkage analysis attempts to locate genes
responsible for a disease using genetic data from a family affected by
that disease. The genetic profile (or genotype) at a number of markers
is determined for as many members of the family as possible. Markers
are identifiable locations on a chromosome (often microsatillite
positions or single nucleotide polymorphisms) where individual humans
are known to show genetic differences. Because the DNA molecule is
linear, these markers can be ordered into a list. Each individual has
two copies of every marker, one from his or her father and one from
his or her mother. Each copy can also be in two possible states,
depending on whether the parent transmitted the marker from his or her
mother or father (the grandparents of the individual).
</P>
<P>To a first approximation, contiguous genes on a chromosome are
generally inherited from the same grandparent. However, meiosis, the
process of cell division which produces eggs and sperm, can alter this
state of affairs. During this process, the parent's two chromosomes
can "cross-over", resulting in two new chromosomes which each contain
a portion of the original two. Cross-over, also known as
recombination, occurs when the phosphate backbones of two DNA helices
with similar sequences break and re-join with each other. Because
recombination occurs between homologous regions of the original
chromosomes, both new chromosomes have a complete set of markers, but
the ancestry of these markers is mixed between the grandfather and
grandmother of the offspring.
</P>
<P>Because such recombination is rare, the closer two markers are on the
chromosome the less likely it is that recombination will separate
them. Two widely separated markers will almost always have at least
one recombination event occur between them and, as a result, will be
inherited together only 50% of the time. Thus, the number of
recombination events that have occurred between two markers is a
distance measure which can be statistically correlated with the
pattern of disease incidence in the extended family. This correlation
gives insight into where on the chromosome the disease gene is located
and is referred to as linkage analysis. Further details of the
Genehunter algorithm can be found in the 1987 paper by Lander and
Green (below). See the following paper for details on our parallel
implementation of Genehunter.
</P>
<P><B>Parallel Genehunter: Implementation of a Linkage Analysis Package for
Distributed-Memory Architectures</B>, G. C. Conant, S. J. Plimpton,
W. Old, A. Wagner, P. R. Fain, T. R. Pacheco, and G. Heffelfinger,
Journal of Parallel and Distributed Computing, 63, 674-682
(2003). (<A HREF = "abstracts/jpdc03.html">abstract</A>)
</P>
<HR>
<P>The modified GeneHunter code can be downloaded from <A HREF = "download.html">this page</A>
</P>
<P>The original Genehunter project was sponsored by MIT's Whitehead
Institute.
</P>
<HR>
<H3>Relevant papers on serial Genehunter:
</H3>
<UL><LI>E. S. Lander, P. Green, Construction of multilocus genetic linkage
maps in humans, <I>Proceedings of the National Academy of Sciences,
U.S.A.</I> <B>84</B> (1987) 2363-2367.
<LI>L. Kruglyak, M. J. Daly, M. P. Reeve-Daly, E. S. Lander, Parametric
and nonparametric linkage analysis: A united multipoint approach,
<I>American Journal of Human Genetics</I> <B>58</B> (1996) 1347-1363.
<LI>K. Markianos, M. J. Daly, L. Kruglyak, Efficient multipoint linkage
analysis through reduction of inheritance space, <I>American Journal
ofHuman Genetics</I> <B>68</B> (2001) 963-977.
<LI>L. Kruglyak, E. S. Lander, Faster multipoint linkage analysis using
fourier transforms, <I>Journal of Computational Biology</I> <B>5</B> (1998)
1-7.
</UL>
<HR>
<H3>Specific details on installing and using our parallel code:
</H3>
<OL><LI>You will need to install the MPI libraries in order to compile our
code.
<LI>Our code can be run on shared memory architectures. However, you will
still need to install the MPI libraries. When compiling the
libraries, specify that the shared memory should be used as the
communication device.
<LI>We modified and tested the multi-point linkage part of Genehunter.
Single-point mode may not work in parallel.
<LI>The makefile will likely need to be modified for your particular
platform. In particular, you will need to give the name of your c
compiler and the location of the MPI library and include files.
<LI>The code is written assuming that the number of processors used is a
power of 2. It cannot be used with other processor counts.
<LI>The user interface has not been changed from the serial version. We
find it useful to write text command files and redirect input to them
from the command line when using Genehunter on a batch system (see the
linkloci.in file included with the parallel genehunter tar file
above).
</OL>
<HR>
<H3>Performance of our code:
</H3>
<P>Both memory and computation is distributed in this implementation.
The figures below give some indication of the scaling performance of
our algorithm for fixed size problems. We computed parallel
efficiency for 3 different problem sizes. For reference, the single
processor runtimes for the 19 and 21 bit problems are 70 minutes and
38 minutes, respectively. The 23 bit problem will not run on a single
processor but requires 34 hours on 2 processors. Panel B gives the
memory scaling for this 23 bit problem (the dashed line indicates
linear memory scaling).
</P>
<CENTER><IMG SRC = "images/genehunter_plot.gif">
</CENTER>
<HR>
<H3>Example files:
</H3>
<P>Genehunter is provided with an example input files (linkloci.dat,
linkped.pre). We have provided a batch script for running this input
file and a couple of our output for verification purposes.
</P>
<UL><LI>linkloci.in
<LI>linkloci.out
</UL>
<HR>
<H3>Contact information:
</H3>
<P>Gavin Conant is the primary contact for questions and problems with
the code. If you cannot reach Gavin, Steve Plimpton can also provide
assistance (sjplimp at sandia.gov). We would be delighted to hear if
this version of Genehunter is helping with your research and to
discuss any ideas you have about the implementation of or
modifications to the code.
</P>
</HTML>