Abstract: Techniques for multiplexed droplet-based sequencing using natural genetic barcodes. An exemplary technique determining a unique variant combination associated with each subject from a plurality of subjects, determining a presence of a plurality of target variants in sequence reads grouped into partitions, and performing a sample demultiplexing and multiplet detection technique (demuxlet) on the sequence reads to: (i) remove sequence reads for partitions that are determined to be doublets based on a first statistical comparison of the unique variant combination associated with each subject and the plurality of target variants in the sequence reads, and (ii) assign a subject from the plurality of subjects to the remaining partitions remaining based on a second statistical comparison of the unique variant combination associated with the each subject from the plurality of subjects and the plurality of target variants in the sequence reads.