Abstract: Methods of isolating nucleic acid and protein molecules from a single formalin-fixed, paraffin-embedded (FFPE) tissue sample section include lysing the cells of the tissue sample section, alkylating, reducing, and enzymatically digesting proteins in the lysate, and separating nucleic acids present in the lysate from the digested proteins. Cell lysis is performed under conditions that permit extraction of DNA, RNA, and proteins that are suitable for genomic and proteomic analysis. In particular, the buffer conditions, reaction time, and temperature of the lysis reaction are such that a suitable amount of DNA, RNA, and proteins are released and in stable condition for separation and proteogenomic analysis. Systems for performing methods include reagents and apparatus for performing steps of the method. Panels for detecting the presence and level of expression of peptides to differentiate between disease states include a plurality of peptides.