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Quantitative analysis on the characteristics of targets with FDA approved drugs.

Sakharkar MK, Li P, Zhong Z, Sakharkar KR - Int. J. Biol. Sci. (2007)

Bottom Line: Accumulated knowledge of genomic information, systems biology, and disease mechanisms provide an unprecedented opportunity to elucidate the genetic basis of diseases, and to discover new and novel therapeutic targets from the wealth of genomic data.Our results show that proteins with 5 or fewer number of homologs outside their own family, proteins with single-exon gene architecture and proteins interacting with more than 3 partners are more likely to be targetable.These quantitative characteristics could serve as criteria to search for promising targetable disease genes.

View Article: PubMed Central - PubMed

Affiliation: ADAMs Lab, Mechanical, Aerospace Engineering, Nanyang Technological University, Singapore. mmeena@ntu.edu.sg

ABSTRACT
Accumulated knowledge of genomic information, systems biology, and disease mechanisms provide an unprecedented opportunity to elucidate the genetic basis of diseases, and to discover new and novel therapeutic targets from the wealth of genomic data. With hundreds to a few thousand potential targets available in the human genome alone, target selection and validation has become a critical component of drug discovery process. The explorations on quantitative characteristics of the currently explored targets (those without any marketed drug) and successful targets (targeted by at least one marketed drug) could help discern simple rules for selecting a putative successful target. Here we use integrative in silico (computational) approaches to quantitatively analyze the characteristics of 133 targets with FDA approved drugs and 3120 human disease genes (therapeutic targets) not targeted by FDA approved drugs. This is the first attempt to comparatively analyze targets with FDA approved drugs and targets with no FDA approved drug or no drugs available for them. Our results show that proteins with 5 or fewer number of homologs outside their own family, proteins with single-exon gene architecture and proteins interacting with more than 3 partners are more likely to be targetable. These quantitative characteristics could serve as criteria to search for promising targetable disease genes.

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Distribution of number of tissues a target is expressed in for percentage of targets with FDA drugs and targets with noFDA approved drugs.
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Figure 2: Distribution of number of tissues a target is expressed in for percentage of targets with FDA drugs and targets with noFDA approved drugs.

Mentions: The mapping of targets with FDA approved drugs and targets with no-FDA approved drugs onto SwissProt knowledgebase and TissueDB was performed, to extract information on the number of pathways a target is involved in and the number of tissues a target is expressed. The distribution of pathway frequency for percentage of targets with FDA drugs and proteins with no-FDA drugs and number of tissues a target is expressed in, is shown in Figure 1 and Figure 2, respectively. Our results shows that, the targets with FDA approved drugs and targets with no-FDA approved drugs, when compared, show no significant bias in the number of pathways involved and the number of tissues a target is expressed (p value = 0.05, implies 95% confidence level) (Table 2).


Quantitative analysis on the characteristics of targets with FDA approved drugs.

Sakharkar MK, Li P, Zhong Z, Sakharkar KR - Int. J. Biol. Sci. (2007)

Distribution of number of tissues a target is expressed in for percentage of targets with FDA drugs and targets with noFDA approved drugs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2140153&req=5

Figure 2: Distribution of number of tissues a target is expressed in for percentage of targets with FDA drugs and targets with noFDA approved drugs.
Mentions: The mapping of targets with FDA approved drugs and targets with no-FDA approved drugs onto SwissProt knowledgebase and TissueDB was performed, to extract information on the number of pathways a target is involved in and the number of tissues a target is expressed. The distribution of pathway frequency for percentage of targets with FDA drugs and proteins with no-FDA drugs and number of tissues a target is expressed in, is shown in Figure 1 and Figure 2, respectively. Our results shows that, the targets with FDA approved drugs and targets with no-FDA approved drugs, when compared, show no significant bias in the number of pathways involved and the number of tissues a target is expressed (p value = 0.05, implies 95% confidence level) (Table 2).

Bottom Line: Accumulated knowledge of genomic information, systems biology, and disease mechanisms provide an unprecedented opportunity to elucidate the genetic basis of diseases, and to discover new and novel therapeutic targets from the wealth of genomic data.Our results show that proteins with 5 or fewer number of homologs outside their own family, proteins with single-exon gene architecture and proteins interacting with more than 3 partners are more likely to be targetable.These quantitative characteristics could serve as criteria to search for promising targetable disease genes.

View Article: PubMed Central - PubMed

Affiliation: ADAMs Lab, Mechanical, Aerospace Engineering, Nanyang Technological University, Singapore. mmeena@ntu.edu.sg

ABSTRACT
Accumulated knowledge of genomic information, systems biology, and disease mechanisms provide an unprecedented opportunity to elucidate the genetic basis of diseases, and to discover new and novel therapeutic targets from the wealth of genomic data. With hundreds to a few thousand potential targets available in the human genome alone, target selection and validation has become a critical component of drug discovery process. The explorations on quantitative characteristics of the currently explored targets (those without any marketed drug) and successful targets (targeted by at least one marketed drug) could help discern simple rules for selecting a putative successful target. Here we use integrative in silico (computational) approaches to quantitatively analyze the characteristics of 133 targets with FDA approved drugs and 3120 human disease genes (therapeutic targets) not targeted by FDA approved drugs. This is the first attempt to comparatively analyze targets with FDA approved drugs and targets with no FDA approved drug or no drugs available for them. Our results show that proteins with 5 or fewer number of homologs outside their own family, proteins with single-exon gene architecture and proteins interacting with more than 3 partners are more likely to be targetable. These quantitative characteristics could serve as criteria to search for promising targetable disease genes.

Show MeSH