Preparation-specific protein groups. Venn diagrams for proteoforms detected in the neat and BCD preparations of (A) normal healthy, (B) NSCLC “Good” and (C) NSCLC “Poor” plasma pools. (D) GO enrichment analysis for molecular functions in the neat preparation-specific proteoforms across NH, NSCLC “Good” and NSCLC “Poor” plasma pools reveals conserved nucleic acid binding capacity. (E) GO enrichment analysis for the BCD-specific proteins showed shared enzymatic functions. Distribution of (F) protein groups detected exclusively with the use of the BCD (red) and (G) protein groups detected exclusively in the neat preparation (blue) compared to 4077 abundance-ranked proteins from the human plasma proteome project (HPPP, build 2021-07, grey). The dotted lines at 0.46 log10 (ng/mL) denote median abundance. (H) Protein groups detected exclusively in the BCD preparation were significantly more abundant in human plasma than protein groups detected only in the neat preparation. Physiochemical characterization of neat- (blue) and BCD-associated (red) protein groups, including (I) molecular weight, (J) pI, (K) hydropathicity and (L) instability index (stable:unstable demarcation of 40 marked in gray). FC, fold change; NH, normal healthy; ns, not significant. ****, p < 0.0001.