Methods, systems and associated computer program products for discriminating type of biological sample of an organism using epigenetic modification information

A computer implemented method for constructing profile of a tissue or a cell, the profile being based on pairs of adjacent epigenetically modified bases, based on epigenetic modification information derived from nucleic acid containing epigenetically modified bases-contained in a sample relating to said tissue or a cell, the method comprising the following steps:

• a) providing digital data on values of epigenetic modification level measurements for epigenetically modified bases contained in said nucleic acid in said sample relating to said tissue or said cell;
• b) determining a set of pairs of adjacent epigenetically modified bases in said nucleic acid contained in said sample relating to said tissue or said cell, each pair of adjacent epigenetically modified bases consisting of two adjacent epigenetically modified bases localized within one nucleic acid molecule so as to generate a map of adjacent epigenetically modified bases containing genomic coordinates of each identified pair of adjacent epigenetically modified bases;
• c) compressing information on epigenetic modification level value, iteratively for each pair of adjacent epigenetically modified bases among the determined set of pairs of adjacent epigenetically modified bases, by converting two values of epigenetic modification level associated with two epigenetically modified bases in each pair, into one single numerical value, said single value representing compressed epigenetic modification information for a pair of adjacent epigenetically modified bases and being indicative of epigenetic modification status in each pair of adjacent epigenetically modified bases;
• d) saving
• genomic coordinates of adjacent epigenetically modified bases for each pair in said determined set of pairs and
• compressed epigenetic modification information in the form of one single numerical value for said each pair of adjacent epigenetically modified bases in said sample so as to generate a profile based on pairs of adjacent epigenetically modified bases of said tissue or said cell;
• wherein each said pair of adjacent epigenetically modified bases is further localized at a distance less than a pre-defined threshold distance.

A computer implemented method for constructing parametrized profile based on pairs of adjacent epigenetically modified bases of a known type of tissue or cell based on epigenetic modification information derived from epigenetically modified base-containing nucleic acid contained in a group of at least one sample, each sample relating to the same known type of said tissue or said cell, the method comprising:

• a) for each sample in said group of at least one sample providing digital data on epigenetic modification level measurements for epigenetically modified bases contained in said nucleic acid in said sample relating to said tissue or said cell of a known type
• b) determining a set of pairs of adjacent epigenetically modified bases in said nucleic acid contained in each sample in said group of at least one sample relating to said tissue or said cell of a known type, each pair of adjacent epigenetically modified bases consisting of two adjacent epigenetically modified bases localized within one nucleic acid molecule so as to generate a map of adjacent epigenetically modified bases containing genomic coordinates;
• then
• c) for said group of at least one sample iteratively for each pair of adjacent epigenetically modified bases among the determined set of pairs of adjacent epigenetically modified bases, compressing information on epigenetic modification level value, by fitting a parametrized mathematical model to said digital data on values of epigenetic modification level measurements associated with each pair of adjacent epigenetically modified bases so as to determine one single model parameter, said single model parameter representing compressed epigenetic modification information for a pair of adjacent epigenetically modified bases and being indicative of epigenetic modification status in each pair of adjacent epigenetically modified bases for said group of at least one sample;
• d) for said group of at least one sample saving
• genomic coordinates of adjacent epigenetically modified bases for each pair in said determined set of pairs and
• compressed epigenetic modification information in the form of one model parameter for said each pair of adjacent epigenetically modified bases in said group of at least one sample
• so as to generate said parametrized profile based on pairs of adjacent epigenetically modified bases of a known type of tissue or cell;
• preferably wherein the epigenetic modification status is one among at least co-epigenetic modification status and non co-epigenetic modification status in a pair of adjacent epigenetically modified bases;

A computing platform for characterizing a test sample from a subject, comprising:

• a computing device comprising a processor, a memory module, an operating system, and a computer program including instructions executable by the processor to create a sample characterizing application, the sample characterizing application comprising a data analysis module configured to:
• a) receive methylation level data provided by measuring methylation level of consecutive nucleic acid sequence contained in said test sample from the subject;
• b) provide for said test sample a CpG pair-based discriminative methylation profile based on methylation level data, wherein the CpG pair-based methylation discriminative profile comprises a differential methylation pairs (DMPs) selected based on specificity of methylation status in said DMPs in at least one sample type among at least one from another sample types, said profile containing genomic coordinates of said consecutive DMPs and a single value indicative of methylation status for said DMPs in said sample;
• wherein said data analysis module further comprises a sample characterizing tool configured to determine sample type, said tool outputting the result of sample characterization and using for characterization one or more pre-established methylation signatures, wherein each of the one or more pre-established methylation signatures correlates with sample type, and wherein each pre-established methylation signature comprises a set of differential methylation pairs DMP selected based on specificity of methylation status in said DMPs in at least one sample type among at least one from another sample types.