A method for controlling for non-systematic error in an amplification-based next generation sequencing (NGS) library preparation, comprising: including an internal amplification control (IAC) that shares identical polymerase chain reaction (PCR) priming sites to a native nucleic acid target template of interest and mimics the kinetics of the native nucleic acid target in the amplification reaction in a NGS library preparation; wherein the IAC controls for non-systematic errors comprises: i) preparing a mixture comprising a known number of internal amplification control (IAC) nucleic acid molecules corresponding to each native nucleic acid target; and ii) mixing the IAC mixture of step i) with a native nucleic acid target-containing sample prior to preparation of a library for sequencing; wherein each native nucleic acid target is similar to its respective IAC, with the exception of one or more changes to the nucleic acid sequence that are identifiable with sequencing, and wherein such changes can include one or more of deletions, additions, or alteration to the ordering or composition of nucleotides used; iii) sequencing the mixture of step ii); iv) assessing the ratio of sequencing events between the native nucleic acid target and its respective IAC, along with the known number of IAC nucleic acid molecules input into the sample prior to library preparation; and v) quantifiably determining the original amount of each native nucleic acid target in the original sample prior to library preparation and sequencing. including an internal amplification control (IAC) that shares identical polymerase chain reaction (PCR) priming sites to a native nucleic acid target template of interest and mimics the kinetics of the native nucleic acid target in the amplification reaction in a NGS library preparation; wherein the IAC controls for non-systematic errors comprises: i) preparing a mixture comprising a known number of internal amplification control (IAC) nucleic acid molecules corresponding to each native nucleic acid target; and ii) mixing the IAC mixture of step i) with a native nucleic acid target-containing sample prior to preparation of a library for sequencing; wherein each native nucleic acid target is similar to its respective IAC, with the exception of one or more changes to the nucleic acid sequence that are identifiable with sequencing, and wherein such changes can include one or more of deletions, additions, or alteration to the ordering or composition of nucleotides used; iii) sequencing the mixture of step ii); iv) assessing the ratio of sequencing events between the native nucleic acid target and its respective IAC, along with the known number of IAC nucleic acid molecules input into the sample prior to library preparation; and v) quantifiably determining the original amount of each native nucleic acid target in the original sample prior to library preparation and sequencing. i) preparing a mixture comprising a known number of internal amplification control (IAC) nucleic acid molecules corresponding to each native nucleic acid target; and ii) mixing the IAC mixture of step i) with a native nucleic acid target-containing sample prior to preparation of a library for sequencing; wherein each native nucleic acid target is similar to its respective IAC, with the exception of one or more changes to the nucleic acid sequence that are identifiable with sequencing, and wherein such changes can include one or more of deletions, additions, or alteration to the ordering or composition of nucleotides used; iii) sequencing the mixture of step ii); iv) assessing the ratio of sequencing events between the native nucleic acid target and its respective IAC, along with the known number of IAC nucleic acid molecules input into the sample prior to library preparation; and v) quantifiably determining the original amount of each native nucleic acid target in the original sample prior to library preparation and sequencing. <EOS>