Average of root mean squared errors of 99 regression models and average of running timings (unit: minute).

<p>Average of root mean squared errors of 99 regression models and average of running timings (unit: minute).</p

Variable selection results: Average of T.P and T.N.

<p>Variable selection results: Average of T.P and T.N.</p

Running timings for regression modeling for <i>σ</i> = 1 via <i>glmnet</i> package in R (unit: minute).

<p>Running timings for regression modeling for <i>σ</i> = 1 via <i>glmnet</i> package in R (unit: minute).</p

Network for selected driver genes and genes having PPI with identified driver genes.

<p>Network for selected driver genes and genes having PPI with identified driver genes.</p

Prediction error: Root mean squared error.

<p>Prediction error: Root mean squared error.</p

Sorted <i>C^dr</i> values of 138 dataset.

<p>Sorted <i>C^dr</i> values of 138 dataset.</p

The estimated frequencies of bases at two 5′ to the mutated site for each cancer type.

<p>The bar heights show the estimated frequency for bases A, C, G and T at the −2 position (two 5′ to the mutated site). The error bars show bootstrapped standard errors. (A, B, C, D, E) The intensities of signature 13 (APOBEC signature), signature 1 (the first Pol <i>ϵ</i> signature), signature 8 (the second Pol <i>ϵ</i> signature), signature 10 (ultraviolet signature) and signature 11, respectively, at the −2 position.</p

Examples of visualizations and parameter values for the mutation signatures of the unconstrained (full) model and our independent model, where substitution patterns, two 5′ and 3′ bases and transcription strand direction are considered as mutation features.

<p>(A) The barplots are divided by 6 substitution patterns and transcription strand direction. In each division, 256 bars show joint probabilities of up to two base 5′ and 3′ bases (ApApNpApA, ApApNpApC, ApApNpApG, ApApNpApT, ⋯, TpTpNpTpT). (B, C) An example mutation signature representation and parameter values from our independent model, where mutation features (substitution patterns, two 5′ and 3′ bases and strand direction) are assumed to be independent (<i>L</i> = 6, <i><b>M</b></i> = (6, 4, 4, 4, 4, 2)). In the bottom five rectangles, the width of each box represents the frequencies of bases (A, C, G and T) at the substitution and flanking site. To highlight the most informative flanking sites, the heights of flanking site boxes are scaled by <math><mrow><mn>1</mn><mo>+</mo><mn>0</mn><mo>.</mo><mn>5</mn><mo>×</mo><mo>log</mo><msub><mo>∑</mo><mrow><mi>n</mi><mo>=</mo><mi>A</mi><mo>,</mo><mi>C</mi><mo>,</mo><mi>G</mi><mo>,</mo><mi>T</mi></mrow></msub><msubsup><mi>f</mi><mi>n</mi><mn>2</mn></msubsup></mrow></math>, where <i>f</i>_<i>n</i> is the parameter for each base, which can be interpreted as 1 − 0.5 × Rényi entropy [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005657#pgen.1005657.ref017" target="_blank">17</a>]. This is analogous to the information content scaling used in sequencing logos. In the top rectangle, the height of each box represents the conditional frequencies of mutated bases for each original base (C and T). In the upper right, the height of the + box represents the frequencies of mutations in the coding strand (the plus strand, the sense strand or the untranscribed strand in other words) whose nucleotide sequences directly corresponds to mRNA, whereas the height of − box represents those in the template strand (the minus strand, the antisense strand, the transcribed strand or the noncoding strand in other words) whose sequences are copied during the synthesis of mRNA.</p

Relationships among mutation signature model, topic models, and population structure models.

<p>Relationships among mutation signature model, topic models, and population structure models.</p

Comparison of prediction accuracy of drug sensitivity.

<p>Comparison of prediction accuracy of drug sensitivity.</p