Figure 5.

Methodological approach to study sex differences in genomics. (A) Perform sex-informed sequence alignment. The framework proposed in the XYalign tool (153), first identifies whether the sequencing reads are derived from an XX or XY genome, considering the balance of reads aligned to X and Y chromosomes. Next, sequencing reads from an XX genome are aligned against a reference genome with the Y chromosome masked, and sequencing reads from an XY genome are aligned against a reference genome masked for regions in the Y that are identical to X, the pseudoautosomal regions (PAR). (B) Use the genomic data to annotate biological sex based on sex chromosome complement. (C) Sex-based analysis may show how the effect of a genomic marker varies between males and females. PCA, Principal component analysis.