Water as a reactant in the differential expression of proteins in cancer

Abstract

The large amounts of proteomic data now available for cancer can used to investigate whether the physicochemical conditions of tumors are reflected in patterns of protein expression and chemical composition. Compositional analysis of more than 250 datasets for differentially expressed proteins compiled from the literature reveals a clear signal of higher stoichiometric hydration state (n H 2 O , derived from the theoretical formation reactions of proteins from particular basis species) in specific cancer types compared to normal tissue; this trend is also evident in pan-cancer transcriptomic and proteomic datasets from The Cancer Genome Atlas and Human Protein Atlas. In marked contrast to cancer, n H 2 O decreases for differentially expressed proteins in hyperosmotic stress (including high glucose) experiments and 3D cell culture compared to monolayer growth. Compositional analysis combined with gene ages (phylostrata) taken from the literature shows higher n H 2 O of human proteins earlier in evolution. Further analyses using amino acid biosynthetic reactions supports the conclusion that a net increase of water going into the reactions of protein synthesis is a biochemical characteristic shared by most cancer types. These findings raise the possibility of a basic physicochemical link between increased water content in tumors and the atavistic or embryonic patterns of gene and protein expression in cancer.

Uncovering chemical signatures of salinity gradients through compositional analysis of protein sequences

“…All metagenomic and metatranscriptomic data analyzed here were obtained from public databases using the accession numbers listed in Supplement Table S1 for salinity gradients and Table S2 for redox gradients. The amino acid compositions of subsampled sequences from the metagenomic and metatranscriptomic data are available in the JMDplots R package, version 1.2.4 (https://github.com/jedick/JMDplots), which is archived on Zenodo (Dick, 2020b). Specifically, the data are contained in the file inst/extdata/gradH2O/MGP.rds, which can be read using the R function readRDS (minimum R version: 2.3.0).…”

“…The charge for each ionizable group was precalculated from pH 0 to 14 at intervals of 0.01, and the isoelectric point was computed as the pH where the sum of charges of all groups in the protein is closest to zero. These calculations were implemented as new functions in the canprot R package (Dick, 2017) (see "Code and data availability" section). Comparisons for selected proteins (UniProt IDs: LYSC_CHICK, RNAS1_BOVIN, AMYA_PYRFU) show that the calculated values of GRAVY and pI are equal to those obtained with the ProtParam tool (Gasteiger et al, 2005).…”

“…S3). This is a major update to an earlier compilation of data for hyperosmotic stress experiments (Dick, 2017), but we have limited the present compilation to data for bacteria or archaea; data for osmotic stress induced by NaCl or glucose in eukaryotic cells are considered in a separate paper (Dick, 2020a).…”

“…Z C is computed from the chemical formulas of organic molecules and takes values between the extremes of −4 for CH 4 and +4 for CO 2 , although the range for particular classes of biomolecules is much smaller (Amend et al, 2013). n H 2 O is derived from the number of water molecules in theoretical formation reactions of proteins from basis species (Dick, 2016(Dick, , 2017. Through the compositional analysis of representative metagenomic and metatranscrip-tomic datasets, we show that Z C and n H 2 O are most closely aligned with environmental redox and salinity gradients, respectively.…”

Uncovering chemical signatures of salinity gradients through compositional analysis of protein sequences

“…The compiled data are available as CSV files in R packages (see Code and data availability). This is a major update to an earlier compilation of data for hyperosmotic stress experiments (Dick, 2017), but we have limited the present compilation to data for bacteria; data for osmotic stress induced by NaCl or glucose in eukaryotic cells are considered in a separate paper (Dick, 2020a).…”