Do It Yourself Pharmacogenomics Biology Essay

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The field of medicine is shifting towards new paradigms owing to the emergence of the discipline of Pharmacogenomics (PGx) which has evolved from a candidate-gene approach to genome- wide association studies (GWASs). PGx defines the implication of genomic variations in the inter-individual inconsistency in response, such as efficacy, dosage and adverse effects, towards a particular drug. Acquisition of this genomic information has been made possible by Rapid High-throughput sequencing technologies which have reduced the cost of whole genome sequencing and have contributed considerably to the development of Personal Genomics.

Genomic Variations, majorly categorized as Mutations and Polymorphisms, can influence either the pharmacokinetic (PK) or pharmacodynamic (PD) drug response pathways. Genetic variations in the PK pathway may affect the absorption, distribution, metabolism or elimination (ADME) of the drug whereas, in the PD pathway may show measurable differences in the response to the drug w.r.t. a particular drug target. So, any change in those genes that encode solute carriers can be considered to contribute towards inter-individual variability in drug uptake. The drug bioavailability can be altered by changes in Export proteins which affect their subcellular localization and transport ability. Many genetic variants have also been reported for changes in the activity of drug-metabolizing enzymes like CYP2C9, CYP2C19, CYP2D6, UGT1A1 etc. which influence drug clearance. All these variations may verify the lack of response to a therapy and also account for the decreased sensitivity to pharmacological agents acting through molecular targets or signalling pathways. Also, many drugs have been found to interfere with the action of others thereby decreasing its efficacy or resulting in undesirable effects. In an independent study in 2004, out of 20,000 admissions to hospital in Merseyside, 1225 i.e. 6.5% were found to be due to ADRs. The study also suggested that around 5700 deaths every year were due to fatal ADRs. Aspirin was the biggest cause of hospital admissions reported, which can cause bleeding in the gut. Reactions to diuretics and the blood thinner Warfarin were also common [10].

Thus, Prior knowledge about the potential drug interaction hazards would prevent people from having interacting drugs together which could have led to potential health hazards. We thereby intend to develop a tool for the analysis of Drug-Drug and Drug-Gene interactions, which could possibly predict the most suitable drug (or combinations) for prescription, based on the individual's genetic make-up.


The main motivation behind developing this computational tool (DIY-PGx) is the increasing emphasis over last few years on providing direct-to-consumer (DTC) services that will bypass experts and give full control to consumers. As of present day, Intellectual Property Rights (IPR) and Gene Patents provide severe roadblocks in developing a diagnostic test or a treatment based on a patented gene. In fact, statistics indicate that more than 25% of labs have abandoned one or more genetic tests due to existing patents [1]. About 20% of human genes are claimed as US Intellectual Property and conflicts have led to an upsurge in regulation of gene patenting laws [2]. Unsurprisingly, many heavily patented genes have a high importance in human health and diseases, some of these being: BMP7, BRCA1, BRCA2 and LEPR [2]. In a recent effort by researchers at University of Maryland, a tool was developed for testing individual genome for mutations in BRCA genes associated with breast cancer [5].

The idea of sequencing a single gene has become outdated because of advances in genomic technology which have led to a rapid downfall in the cost of sequencing complete genomes. With companies like Myriad Genetics charging about $3000 for tests of the BRCA genes, today the overall cost of sequencing an entire genome is less than $20000. Various companies like Knome, Lumigenix, deCODE genetics, Existence genetics, Navigenetics, 23andMe etc. are providing services that index distinct DNA sequence variations correlated with a genetic condition and provide every chunk of information about the entire 6 billion base-pair genetic sequence.

With constant support from the informatics community it would soon be possible to store completely sequenced genome in a digital form either as gene-cards [3] or in smartphone's [4]. These can then be referred in future by the doctors to evaluate the risk of new diseases upon identification of new disease-causing mutations and various other useful interpretations like likelihood of drug reactions, efficacy of specific drugs etc could be made.

With this preview, we have developed an open source freely available online software "Do It Yourself-Pharmacogenomics" (DIY-PGx) which helps users to analyse their genomes using the manually curated dataset containing comprehensive information of pharmacogenomic data for drugs and biological markers. The only requirement is a pre-sequenced genome in order to predict suitable drugs and their responses based upon individual's genetic information. This software is ahead of its time and will serve as a ready to use tool for interpreting user genomes.

About DIY-PGx

Developing this software required an extensive literature survey and an arduous process of collecting sufficient information regarding various drugs, their metabolic pathways and mode of action and then the effect of various biomarkers on them was studied.

Based on this information, we curated an exhaustive list of drugs and the related biomarkers affecting their metabolism. The effect of the genetic variants on the activity of the drug was recorded and analysed to predict the comparative effectiveness of drugs for a particular genotype.

Currently, as the search for markers related to a drug and their effect on drug efficacy and toxicity requires access to several websites, so we have also considered the need for an integrated database which allows linking of information, and overcomes the need for website hopping. This system has been developed with an aim to help researchers in determining potential biomarkers, and to allow ease of analysis on available data from various sources.

DIY-PGx offers a very informative and easy-to-use interface for users to upload their genomic data. It also provides users with a feature to upload their genomic data in multiple file format types, as provided to them by various Genome sequencing companies. The input file must contain a list of Single Nucleotide Polymorphism (SNP) identifiers i.e. rsid as given in dbSNP build 134. The interface reads the user inputted genomic data and then interacts with the built-in databases and interprets the matches providing detailed information regarding the potential effects of drugs. The user can thus, browse through different markers to find the most suitable drug based upon his/her genetic constituent. We assure complete privacy to users allowing them to analyse their genome anytime and from anywhere. Drug prescription would be as simple as measuring body temperature or blood pressure and would just take few computations.

3.1 Tools and Utilities

DIY-PGx provides a handful of interesting tools to interpret the genomic data.

The Drugs section provides a graphical overview of the drugs associated with specific SNPs by plotting horizontal bars for each Drug-SNP pair utilizing the odds ratio. Thus a list of several such bars would be generated considering multiple interactions between drugs and SNPs.

The Disease section provides a tabular display for various diseases in which a particular SNP has been reported in literature.

The Adverse Drug Reactions (ADRs) section gives a tabular output listing out the several ADRs related to the use of a particular drug.

The Conditions section provides an overview of various drug phenotypes resulting due to a SNP.

3.2 Interface

A user friendly and easy to use web-based graphical interface has been designed using Asp.NET language. Data handling is achieved using SQL queries. The data is easily connected using PHP to MYSQL queries using the PHP-SQL functions. The homepage (Figure 1) provides the user with an option to upload his/her genomic data, a menu that enlists the tools (discussed above) and the contact details. The software is made available at for public use.


Today the gene-centred approach of genetic testing seems far more expensive than entire genome sequencing and efforts like those to make gene-cards could come in handy.

Having an e-genome would give the freedom to exploit the vast amount of data in numerous biological databases and make interesting interpretation. This would also give consumers the power to analyse their genome themselves without having to get their genomes sequenced. Do it yourself techniques have grabbed high attention of researchers in recent times and has even raised a point for debate. Critics believe that giving full power to analyse very complex molecules such as genomes to those with little or no knowledge can be very harmful for the society and can result in epidemic. Though DIY techniques hold a strong promise, a lot of ethical issues must be resolved to convince its existence.

DIY-PGx is intended for research and educational purpose only and should not be considered as a diagnostics report. Its interpretations are not regulated by any medical agency and users are encouraged to consult their physicians for any medical concerns. Although genetic variants may have a significant impact on drug metabolism, they do not work in a vacuum. Drug response can also be affected by age, weight, race, comorbidities, diet and other drugs or supplements an individual might be taking. Other relevant factors should not be ignored in the face of pharmacogenomic information.