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Table 3
Comparison of available technologies for identification of microbial sequences in human tissues
(A) Genomic DNA-based platform vs. RNA-based platform

Platform	Principle for Analysis	Advantages	Disadvantages	References

RNA-based	Extraction of sequences from expression library data sets	Detection of actively expressed microbial genes regardless of DNA copy number	No detection of non-transcribed microbial genes	Computational Subtraction [14,16]
		Tags can be generated as long as genes are transcripted	Can miss detection if low microbial load	DTS [17,21]
		Tag numbers are not limited by the genome size	Subject to sequencing errors or tag site polymorphisms matching microbial sequences	Viral Detection DNA Microarray [8]
				RDA [13]

Genomic DNA-based	Extraction of sequences from genomic library data sets	Detection of microbial DNA regardless of expression status of the genes	No detection of non-reverse transcribed RNA	DK-MICROBE
		Potential to detect latent microbial genomic fragments which have been integrated into human genome	Can miss detection if low microbial load	Computational Subtraction [15]
		Utilization of clinical samples not suitable for RNA extraction including paraffin-embedded fixed tissue	Subject to sequencing errors or tag site polymorphisms matching microbial sequences

(B) Tag-based vs. array hybridization

Platform	Principle for Analysis	Advantages	Disadvantages	References

Array hybridization	Cross hybridization to homologous sequences of microorganisms on microarray	Currently lower cost	Array designed to target limited number of candidate microbes	Viral Detection DNA Microarray [8-11]
		Method is highly versatile and generally high throughput	Risk of unspecific binding

Tag-based	Fractional representations through extraction of sequences from specific locations in microbial genomes	Sequence based non biased result	Limited by sequencing costs	DK-MICROBE
		Greater chance to identify rare microbial associations	Subject to sequencing errors, tag site polymorphisms	Computational Subtraction [14-16]
		No physical generation of organism-specific array		DTS [17,21]
		Results can be utilized and referenced for additional human genome analyses

A. Advantages and disadvantages of using genomic DNA- versus RNA-based platforms. B. Advantages and disadvantages of using tag-based versus array hybridization platforms. Abbreviations: DTS, digital transcript subtraction; RDA, representational difference analysis.
Duncan et al. BMC Medical Genomics 2009 2:22 doi:10.1186/1755-8794-2-22

Table 3