Abstract: Methods and systems for generating a personalised pharmacodynamic profiles for an individual subject are provided. The method comprises the steps of: isolating total cell free RNA (cfRNATOTAL) from a liquid biopsy obtained from the individual subject and identifying an amount of at least a first cell free RNA (cfRNA) present in the liquid biopsy, wherein the first cfRNA encodes a first protein that has a pharmacodynamic activity. From the amount of cfRNA in the liquid biopsy an amount of the first protein in the individual subject can be determined, thereby allowing a personalised pharmacodynamic profile for the individual subject to be generated. The methods and systems find utility in precision dosing and personalised medicine.

Abstract: Processes are provided for establishing a virtual physiologically based pharmacokinetic (PBPK) model in a population comprised of a plurality of individual subjects that has been or may be exposed to a xenobiotic molecule. The processes are derived from the identification of an abundance of a protein that is involved in absorption; distribution; localization; biotransformation; and excretion of the xenobiotic molecule from a liquid biopsy of corresponding cell free RNA. Personalised PBPK models for precision dosing, as well as methods of treatment are also provided.

Abstract: An assay method is provided for determining the status of the health of a tissue within the body of a subject, wherein the tissue comprises an abundance of at least a first target protein, wherein assay comprises analysis of a liquid biopsy sample obtained from the subject, and wherein the liquid biopsy sample comprises at least a first cell free mRNA (cf-mRNA) that encodes the at least a first target protein. The assays and methods are useful in the diagnosis and treatment of liver health in a subject. In particular, methods and systems are provided for the diagnosis and treatment of fatty liver; non-alcoholic steatohepatitis (NASH); cirrhosis; liver disease; hepatitis; and liver cancer.

Abstract: Methods, systems and apparatus are provided for quantifying the amount of at least a first cell free RNA (cfRNA) present in a liquid biopsy obtained from an individual subject. The first cfRNA may encode a protein that functions in the clearance of xenobiotic compounds from the body of the subject. Quantification of the amount of the first cfRNA is normalised to the individual and permits the construction of more accurate virtual models that facilitate improved personalised medicine, dosage regimens and clinical trials.