Described and provided herein are methods and systems useful for the analysis of polynucleotides and/or detection/quantification of cancer risk identifiers for cancer screening. For example, in certain instances, the methods and systems described are useful for determining changes in the rates of genetic change (e.g., mutation accumulation as a function of time) and/or epigenetic changes (e.g., methylation status change as a function of time), which can be used to profile the risk that an individual has cancer or is likely to develop cancer.