Systems and Methods for Additive Genomic Sequencing With Cumulative Coverage and Longitudinal Analysis

A method for additive genomic sequencing comprising:

• obtaining a plurality of biological samples from a subject at predetermined time intervals;
• performing sequencing on each of the plurality of biological samples to generate a plurality of sequencing datasets, each sequencing dataset having a defined coverage depth;
• aligning each of the sequencing datasets to a reference genome to generate a plurality of aligned datasets;
• merging the plurality of aligned datasets to generate a cumulative sequencing dataset having a cumulative coverage depth, wherein the cumulative coverage depth is substantially greater than the defined coverage depth of any individual sequencing dataset;
• and
• analyzing the cumulative sequencing dataset to identify genomic variants present in the subject.

A computer-implemented method for integrating temporal genomic data, comprising:

• receiving a plurality of sequencing datasets generated from biological samples collected from a subject at different time points;
• processing each of the sequencing datasets through a standardized bioinformatics pipeline to generate aligned read data and variant call data for each time point;
• implementing batch effect correction to minimize technical variations between the sequencing datasets collected at different time points;
• aggregating the aligned read data from each time point to generate a cumulative coverage dataset;
• performing variant calling on the cumulative coverage dataset to identify genomic variants;
• tracking allele frequencies of the identified genomic variants across the different time points;
• and
• generating a longitudinal profile of genomic changes in the subject based on temporal variations in the identified genomic variants.