Methods and systems for processing nucleic acid molecules

A method for processing a plurality of nucleic acid molecules, comprising:

• (a) subjecting a nucleic acid molecule of said plurality of nucleic acid molecules to a nucleic acid amplification reaction, wherein said nucleic acid amplification reaction is performed in presence of at least one nucleotide analog, thereby generating an amplified nucleic acid molecule comprising said at least one nucleotide analog;
• (b) contacting said amplified nucleic acid molecule with a modification dependent restriction enzyme;
• (c) using said modification dependent restriction enzyme to subject said amplified nucleic acid molecule to fragmentation at a location at or in proximity to said at least one nucleotide analog to yield a plurality of nucleic acid fragments;
• and
• (d) using a nucleic acid barcode molecule comprising a barcode sequence to barcode a nucleic acid fragment of said plurality of nucleic acid fragments, to yield a barcoded fragment comprising said barcode sequence.