Additional file 3: of An evaluation of processing methods for HumanMethylation450 BeadChip data

Multidimensional scaling plot of distances between samples in COAD, scaling dimensions 1 vs 2, samples colored by plates. Euclidean distances between sample pairs are computed for a common set of 5000 features having the largest standard deviations across all samples. Features containing SNPs or mapping to the sex chromosomes were excluded. (PDF 7 kb

Additional file 1: of At least two well-spaced samples are needed to genotype a solid tumor

SOM: LOH can confound mutation classification. (DOCX 423 kb

Additional file 2: Figure S1. of At least two well-spaced samples are needed to genotype a solid tumor

Data from the 8 tumors not in Fig. 2. (PDF 223 kb

Additional file 4: of An evaluation of processing methods for HumanMethylation450 BeadChip data

Density distributions of Beta values for the Type I (solid lines) and Type II (dashed lines) probes for six PBLs replicates under different processing methods. (PDF 50 kb

Additional file 3: of Data integration by multi-tuning parameter elastic net regression

The optimal penalty ratio parameters versus the change of (A) number of correlated features in the second data type; (B) correlations among features in the second data type; and (C) correlations among features between different platforms. Dots represent the mean of optimal weights and caps represent the standard error of the mean; N = 200 simulation replicates. (PNG 100 kb

Gene conservation signals drug vulnerabilities.

A) Targeted EGFR drug sensitivities (z-scores, negative values more drug sensitive) correlated with EGFR conservation (z-scores, negative values more conserved). Most drug sensitive cell lines showed preferential targeted gene conservation with r-shaped distributions. B) Conservation of BCL2 (venetoclax), ALK (crizontinib), and FLT3 (midostaurin) correlated with their cell line targeted therapy sensitivities.</p

DepMap essential genes exhibit preferential epigenetic conservation.

A) Diagram of how drift and selection cause preferential epigenetic conservation. Initially identical daughter cells acquire epigenetic differences from drift. Cells with more optimal epigenomes (green) will be more fit and dominate the population. Once an epigenome is optimized, negative selection will tend to conserve the favored epigenetic configuration because variants are lost. Drift still occurs but changes are more tolerated in less functional genes, leading to preferential conservation of the genes under selection. The more essential a gene is to cell survival, the greater the selection and conservation. Circles indicate CpG sites, with filled circles indicating DNA methylation. B) Gene DNA methylation varies between two samples of the SW620 CRC cell line cultured in the USA and Spain. Smaller differences in methylation are present for DepMap essential genes (blue dots). C) DepMap essential genes (shRNA log-fold decrease less than -0.4) showed significantly smaller gene PWDs than non-essential genes. D) Essential genes are significantly more conserved (lower PWDs) than non-essential genes (red symbols) in tissue culture and normal colon crypts. Essential and non-essential genes in colon crypts were significantly less conserved than after 20 months of serial passage of a clonal cell line (p E) Essential DepMap genes are also significantly more conserved in normal human colon. Conservation differences are greater between normal adult colon crypts than between cell lines samples, likely reflecting the many more divisions that occur with aging relative to tissue culture. Most curated genes (red circles) important to colon crypt biology by other experimental criteria [10] are not essential by DepMap gene disruptions, but show preferential conservation, with gene PWDs less than 0.1.</p

Additional file 2: of Data integration by multi-tuning parameter elastic net regression

The accuracy in testing dataset, sensitivity and specificity of feature selection from Standard EN and MTP-EN for different simulation settings. MTP-EN achieves better classification and sensitivity in Scenarios 1–3. (PNG 214 kb

Tissue specific gene conservation and conserved gene expression.

A) Conservation differences are greater between colon crypts and endometrial glands than between colon and SI crypts. This variation is less for DepMap essential genes (red circles). Gene exhibiting differential tissue conservation may be important for tissue specific cell survival. B) Homeobox genes are enriched in differentially conserved endometrial versus colon comparisons. HOXA genes (blue circles) are preferentially conserved in colon crypts whereas HOXB genes (green circles) are preferentially conserved in endometrial glands.</p

Epigenetic drift and conservation.

A) Epigenetic drift occurs in all genes. Conservation progressively decreased between clonal cell lines started from a single colorectal cancer cell (HCT116) and passaged in triplicate. Differences between essential and non-essential genes are minimal after 2.5 months. Conservation decreases slightly for the essential genes but non-essential genes drift more by 14 months. The 14 and 20 month time points are similar (also see Fig 1D). B) PWDs between mock treated and AZA treated cultures (averages of 14 CRC cell lines). AZA treatment initially decreased conservation, but conservation progressively increased during the 21 days after DNA demethylation. The trend is marginally significant for the non-essential genes (p = 0.049) but not for DepMap essential genes (p = 0.11). C) PWDs between control and an AZA treated HCT116 CRC cell line. AZA also decreased conservation, and conservation progressively increased during the 68 days after DNA demethylation. The increase in conservation is significant for DepMap essential and non-essential genes (pD) The increase in conservation with time after AZA treatment for the HCT116 CRC cell line contrasts with the decrease in conservation after single cell cloning (Fig 2A). E) Epigenetic conservation is stable with human aging in colon crypts. The trends for decreased conservation with aging are not significant.</p