Technology Overview

Population Diagnostics (PDx) has developed a platform technology for high-throughput discovery and validation of “causative” genetic biomarkers.  Causative biomarkers are the only biomarkers that can be used to develop molecular diagnostic tests because they indicate with certainty that an explicit genetic condition is present or will eventually develop in a patient.  Additionally, a causative biomarker is a beacon for a biological pathway and is a prerequisite for developing targeted therapeutics.  PDx is establishing the industry standard for personalized medicine by defining and bringing to market the clinical value of causative biomarkers.

PDx’s technology solves a major problem obstructing the biomedical industry’s ability to translate biomarkers into clinical products that address unmet medical needs.  The reality of the last decade in human disease research, which was predicated on the Common Disease – Common Variant hypothesis, is that most single nucleotide polymorphisms (SNPs) have negligible clinical value as biomarkers.  At best, the SNPs used in genome-wide association studies (GWAS) can only be used to infer slight increases in disease incidence and are often described as “predisposition,” “risk,” or “susceptibility” factors.  They cannot be used in clinical diagnostics tests and are unlikely to be signposts for biological pathways of interest.  Essentially, a diagnostic test using biomarkers that are not considered “causative” will result in physicians and patients making baseless medical, dietary, and quality of life decisions.  If used in pharmaceutical development, the resulting drugs will not be effective or safe in the majority of eligible patients.

PDx’s genome-wide biomarker discovery platform systematically and rapidly reveals rare genetic variants.  When applied to the study of common diseases, comprehensive collections of causative mutations are found, which can be used to develop early detection diagnostic tests and provide pharmaceutical companies with a greatly expanded number of drug targets to fuel drug discovery (e.g., RNAi R&D programs).  In drug development, responders, non-responders, and serious adverse events can be differentiated with rare genetic variants; thus, enabling the systematic development of companion tests for drugs.

PDx’s technology rationally interprets human genomes primarily by considering the vast spectrum of “normal” variation within an ethnically diverse population in order to sift out the small fraction of variants unique to a disease or drug profile.  Personalized medicine will advance only when genetic subgroups are defined by rare genetic variants.  At the heart of our rare variant discovery platform are recent evidence-based principles of genome biology, such as:

  – Any two genomes differ at least 10-fold more than previously thought.  Thus, human genetic diversity is    

     greater than anyone imagined, which magnifies the complexity of disease research.

 

  – Copy number variants (CNVs) and other structural variants have a major contribution to genetic variation and  

     are frequently found in healthy people and those with disease (e.g., autism, schizophrenia, and Parkinson’s).

 

  – Many disease-causing mutations are not inherited, but are “de novo” (occurring for the first time in an     

     individual) and assessing their frequency in the population is important to understanding missing heritability.

 

  – Rare genetic variants, often in the form of CNVs, have recently been found to play a larger role in diseases  

     than previously known.

 

  – Common diseases are heterogeneous (many diseases masquerading as one) and multigenic; that is, the     

     disease phenotype (symptoms) can be caused by different genes/mutations but each individual has one main

     independently causal rare variant.

 

  – Ethnic diversity must be integrated into biomarker discovery.  Using only homogeneous populations (e.g., 

     Canadian founder, Icelandic, and Utah cohorts) in studies will not yield clinically relevant biomarkers applicable      in the population at large.

 

  

 

 

 

 

 

 

 

 

 

 

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