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21. Takahashi, K., Yugi, K., Hashimoto, K., Yamada, Y., Pickett, C.J., and Tomita, M. 2002.
Computational Challenges in Cell Simulation: A Software Engineering Approach. IEEE
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Email: ramuigib@gmail.com
Abstract
M. tuberculosis is a dreaded pathogen causing the respiratory disease Tuberculosis with high rates of
mortality (approximately 1 death per 1.5 min. in India alone). The rate of susceptibility to M.
tuberculosis infection is extremely high. The circulation of drug resistance strains aggravates this
problem several folds higher. While considerable efforts are focused on identifying drug targets and
new vaccine candidates, novel strategies and new molecules are required to continuously battle with
the problem of drug resistance. In this scenario, it is very important to carry out systems modeling
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Figure 1. The Knowledge Elevation Path of systems biology for biologists in the post genomics era.
The Systems Biology data in R is at the second stage of this knowledge elevation path.
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print(ORFFunctions[i,])}}
here n is the no. of entries in x, which can be obtained using the command length(x).
(ii)
(iv)
What are the genes in a certain pathway? The relevant dataobject is PathwayReaction
Running the following script will give the results
for (i in 1:952) { if (as.character(PathwayReaction[i,5]) == "Purine metabolism" )
print(paste(PathwayReaction[i,1]," ",PathwayReaction[i,5]))}
Caution: may get redundant entries because of KEGG data
(v)
If we want to check for essential and non polymorphic Rv nos. this can be done by
selecting essential and leave out the known polymorphic ones and running the
following scripts
x<- union(SNPintragenic[,1],SNPintergenic[,1])
x<- union(x,InDelintragenic[,1])
x<- union(x,InDelintergenic[,1])
y<- HighProbabilityOfEssentialGenes[,1]
z<- setdiff(y,x)
z
The dataobject z contains the Rv nos. as per requirement. Caution: The results are
strongly dependent on the known data on polymorphisms in genes, therefore
absence of data does not automatically conclude absence of polymorphism.
However, the known polymorphic genes will be certain to be excluded by this
approach.
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If we want to use the Bioconductor as one example where we wish to get the
sequence of a given Rv id is
> library(Biobase)
> getSEQI(as.numeric(Rv2GI[1,2]))
Output is the sequence. Extending this further for example, the following command
can be used to get sequences of multiple Rv nos. using functions from
Bioconductor. For example one could combine queries from above and link to this
script to obtain sequence data along.
for (i in 1:3989) { for (j in 1:3) {if (as.character(Rv2GI[i,1]) == as.character(x[j]) )
print(getSEQ(as.numeric(Rv2GI[i,2]))) }}
(vii)
x<- NULL
for (i in 1:3997) {if(as.numeric(as.character(SurfaceAdhesion[i,2])) >= 0.7) x<cbind(x,as.character(SurfaceAdhesion[i,1]))}
z<- intersect(x[1,],as.character(MtbPersistance[,1]))
w<- NULL
> for (i in 1:4686) {for (j in 1:8) {if
(as.character(MtbStrainWiseExpressionZScores[i,1]) == z[j]) w<rbind(w,MtbStrainWiseExpressionZScores[i,])}}
(ix)
Can we get ORFids belonging to one pathway having high Drug Target Rank and
with known interactions in Human host? Example glycine, serine metabolism
pathway and assuming 100 is a high drug target rank, we have
x<- grep("^glycine,serine", PathwayReaction[1:952,5], ignore.case=TRUE)
y <- NULL
for (i in 1:26) {m<- x[i]; y<- cbind(y, as.character(PathwayReaction[m,1]))}
> z<- NULL
> for (i in 1:3927) {if (as.numeric(as.character(DrugTargetRank[i,2])) >=100 ) z<c(z,as.character(DrugTargetRank[i,1]))}
temp<- intersect(z,y)
result<- intersect(result, as.character(HumanMtbProteinInteractions[,1]))
Conclusion
At present different types of data on M. tuberculosis and tuberculosis related topics
have to be sourced from different sites. Besides these data will have to be organized in proper
formats so that they can be further analyzed through other algorithms and software. The
initialization of M. tuberculosis Sysborg in R aims to bridge all these gaps. However, we may have
some shortcomings in that all data tables may not have been packaged. This is due either to
restricted access or data distribution control issues. The present data provided is the publicly
available data. However, users can package their own data or other publicly available data and make
their own package. In this sense, this platform truly adheres to the basic tenets of open source.
Relevant data for modeling can also be extracted with simple commands and fed as input in to
programs like CellDesigner for simulation work. One can also use the deSolve package from R to
solve differential equations giving identical results. As shown above, one can also use the functions
of Bioconductor or KEGGgraph to get additional information or carry our further analysis. As
more analysis packages appear in R, they can be integrated with M. tuberculosis SysBorg thereby
enhancing the capabilities further. We as authors envisage many more developments by bright young
minds in order to contribute effectively to Tuberculosis research.
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Introduction:
Malaria is a prehistoric disease. It is believed that malaria may have contributed to extinction of
dinosaurs from the earth. There is documentation of malaria in our old civilizations, Egyptian
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