The duration of proteinase K exposure affects the evenness of genome-wide read distribution. (A) For five different durations of lysis (10, 30, 60, 120 min, and overnight (O/N)), the evenness of coverage is determined by calculating the number of 20 kb windows and the number of sequencing reads therein. The y-axis displays the genome-wide number of windows (X 1,000) while the x-axis depicts the number of quantile normalized reads. The width of the curve shows the genome-wide variation in read-depth between all windows. (B) Zoomed-in region of (A) to illustrate the read differences in windows with relatively difficult to cover genomic regions. (C) Genome-wide tissue-specific differences in read-depth per window are displayed for brain and liver at four different durations of lysis (30, 60, 120 min, and overnight). (D) Comparison of the genome-wide read distribution for a sample treated 10 min with proteinase K (blue line), and the exact same DNA sample after 120 min of extra proteinase K treatment (black line).