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%% This document created by Scientific Word (R) Version 3.5

%TCIDATA{LastRevised=Thursday, January 03, 2002 16:54:56}
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\title{A Note on Applications of Support Vector Machine}
\author{Seung-chan Ahn}
\address{Fermilab, MS 360, P.O. Box 500, Batavia, IL 60510}
\author{Gene Kim}
\address{93B Taylor Ave, East Brunswick, NJ 08816}
\author{MyungHo Kim}
\address{93B Taylor Ave, East Brunswick, NJ 08816}

We describe in a rudimentary fashion how \emph{SVM}(support vector machine)
plays the role of classifier in a mathematical setting. We then discuss its
application in the study of multiple \emph{SNP}(single nucleotide
polymorphism) variations. Also presented is a set of preliminary test results
with clinical data.



It is a generally accepted wisdom that the causes of biological effects can be
divided into two categories - inhritable(genes from parents) and
environmental(food, gravity, sunlight, surroundings etc). In this paper, we
focus on inheritable factors. Our suggestion to multiple \emph{SNP} variations
is based on the following general assumptions(For more details, see \cite{KK}).

\item[1] \emph{Suppose all the SNPs are known and there are no environmental
factors. Then each human is determined by a complete set of SNP variations uniquely.}

Its consequences are: identical twins are exactly the same. Thus it is
possible to classify \emph{SNP} data sets into several subgroups.
Classification(grouping or clustering) is one of basic and important generic
method for distinguishing one from another.

\item[2] \emph{To classify objects we are interested in, the most powerful
technique people developed is to numericalize them, in other words, finding a
way of representation into numbers and the collection of numbers into vectors
in a Euclidean space.}

The two assumptions are separately common senses among researchers. The new
twist is that the two assumptions were not considered in the same scope and
\emph{SVM} offers a powerful machinery to tackle the problem of classification
in a rigorous and systematic way.

\section{Support Vector Machine and Its Analogy}

The concept of \emph{SVM}(Support Vector Machine) was introduced by
Vapnik(\cite{Va}) in the late 1970's. Since then the idea of \emph{SVM} found
its application in many diverse fields such as machine learning, gene
expression data analysis, high energy physics experiment at \emph{CERN}
(European Organization for Nuclear Research). Why the idea of \emph{SVM} has
been used in such diverse and unrelated fields ? The reason is clear and
obvious: \emph{SVM}, based on a solid mathematical foundation, attempts to
solve a universal problem of classification, i.e., we need to know which
belongs to which group. The basic idea of \emph{SVM} is deceptively simple.
Given a collection of vectors in $R^{n},$ labeled +1 or -1 that are separable
by a hyperplane, \emph{SVM} finds the hyperplane with the maximal margin. More
precisely, the distance between the closest labeled vectors to the hyperplane
is maximal.(Vapnik, cleverly, connected this distance problem to an
optimization problem by using Kuhn-Tucker condition, \cite{Si}). This
hyperplane could be used to determine to which group an unlabeled vector
belongs. This machine fits with inductive scientific method.

To give you a definite flavor of \emph{SVM} in everyday experience, let's
consider about familiar concepts , speed limit, height,weight, blood pressure,
Lipid measurements in blood etc. When the speed limit, critical values for
blood pressure of normal people, Lipid mesurements are determined, people
mainly depend on experimenatal data in the past. As a toy model, we considered
an analogy or correspondence between finding the speed limit on the road and
using Support Vector Machine for a criterion to determine an association
between a given set of multiple SNP variations and a disease or trait.

In mathematical setting, car speed is a point in $R^{1},$while a set of
numbers consisting of SNP variations(or anything we count several variables at
the same time) is represented as a point of $R^{n}$.


\put(54,10){\makebox(0,15){\sl Speed}}%

\put(54,10){\makebox(0,-10){\sl A Single Number}}

\put(90,10){\makebox(0,15){\sl Feature Vector}}%

\put(90,10){\makebox(0,-10){\sl A Set of Numbers}}


\hspace{1.0in}$\Downarrow$\hspace{2.3in}$\Downarrow$ \newline \hspace{1.0in}

\put(5,-15){\framebox(110,50){{\sl By Simple Statistic}}%
\put(5,0){\framebox(110,50){{\sl Speed Limit}}}
\put(30,-15){\framebox(150,50){{\sl By Support Vector Machine}}%
\put(30, 0){\framebox(150,50){{\sl Hyperplane of Criterion}}}%


\hspace{1.5in} \hspace{1.5in} \newline \newline 

\item[Conclusion] We come to the conclusion that we have to find out a way of
representation of \emph{SNP} variataions at each position. This subject is
open and could be adjusted with experiments for better
performance.\footnote{After we found out to use the \emph{SVM} to classify
multiple SNP variations, Honki Kim, statistician, pointed out that
Classification tree(or decision tree) might work as well.} Suppose we want to
express east, west, south and north(or DNA letters, \emph{A, C, G, T}). Then
we may represent them as $\{(1,0,0,0),(0,1,0,0),(0,0,1,0)$, $(0,0,0,1)\}$ or
$\{0.2,0.4,0.6,0.8\}$. This way, at each SNP location, we have a number
depending on genotype in a consistent way, which give us a vector.

\section{Test Results with clinical data}

We generated feature vectors of cardio-patient records by using the same
principle described in \textbf{section 2}. Height, age, sex, weight, ethnic
background, medical history, birth place, blood pressure(systolic and
diastolic), Lipid measurements etc are numericalized and we labeled +1 for a
patient who had a history of either heart attack, stroke or heart failure,
otherwise -1. We used Thorsten Joachims' implementation of \emph{SVM}, which
gives us the following results(See \cite{Jo} and, for a different
implementation, \cite{Van}). The results strongly indicate that \emph{SVM}
works as intended to separate the data set into two classes.

Test & No of Patients & +1 labeled & -1 labeled & C(bound) & Misclassified &
postoneg & negtopos\\\hline
1 & 1000 & \ \ 212 & \ \ 788 & \ \ 1 & \ \ 56 & \ \ 32 & \ \ 24\\
2 & 1000 & \ \ 212 & \ \ 788 & \ \ 2 & \ \ 41 & \ \ 23 & \ \ 18\\
3 & 1000 & \ \ 409 & \ \ 591 & \ \ 1 & \ \ 153 & \ \ 37 & \ \ 116\\
4 & 4000 & \ \ 1055 & \ \ 2945 & \ \ 1 & \ \ 438 & \ \ 168 & \ \ 270\\\hline
\caption{Tests with clinical data}%

For the summary of tests, see the Table 1.

\item[1] Postoneg means the number of +1 labeled vectors in the group of -1
labeled majority, while negtopos the number of -1 labeled vectors in the group
of +1 labeled.

\item[2] Test 1 and 2 are the same data with different C values.

\item[3] Test 1 and 3 are different.

\item[4] Test 3 is contained in Test 4.


Support Vector Machine can be applied for diagnosis of diseases and drug
adverse. If, for each possible patient, we input all the test results as a
vector, the status of a disease and its prescription could be determined from
the past disease records. It should be noted that the data is not limited to
numerical ones and it could include visual data such as X-ray or MRI image and
possibly other sources. For example, in the image data, one extracts area,
length, its topological invariant and others for the totality of input data.

Due to its generic nature of \emph{SVM} already found its application in
diverse field and it may find even more application elsewhere. (Depending on
the users's insight and intuitions, for example, putting genotypes with
phenotypes, drug and phenotypes or genotyes etc.)


We are grateful to thank to Profs Larry Shepp of Rugers University, Chul Ahn
of University of Texas at Houston and Dr. Honki Kim of Cedent Corp. for
comments and criticism. Special thanks are due to Prof. Vanderbei at Princeton
University for demonstration of his software implementation of \emph{SVM}.

\begin{thebibliography}{9}                                                                                                %
\bibitem[1]{Jo}Joachims, Thorsten, Making large-Scale SVM Learning Practical.
Advances in Kernel Methods - Support Vector Learning, B. Sch\"{o}lkopf and C.
Burges and A. Smola (ed.), MIT Press, 1999.

\bibitem[2]{KK}Kim Gene and Kim, MyungHo. Application of Support Vector
Machine to detect an association between a disease or trait and multiple SNP
variations, (

\bibitem[3]{Si}Simmons, Donald, Nonlinear programming for operations research,
Prentice Hall, 1975

\bibitem[4]{Van}Vanderbei, Robert. rvdb

\bibitem[5]{Va}Vapnik, Vladimir. The Nature of Statistical Learning, Springer,
New York, 1995

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