1. Visualizing Clonal Evolution in Cancer
Martin Krzywinski 
Molecular Cell 
Volume 62, Issue 5, Pages (June 2016)
DOI: /j.molcel
Copyright © 2016 Elsevier Inc. Terms and Conditions

2. Figure 1 A Qualitative Tumor Clone Evolution Diagram
The placement and choice of slightly asymmetric shapes representing the clones emphasizes that the diagram is qualitative and not quantitative (Chun et al., 2013).
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

3. Figure 2
Clone Evolution Diagrams Effectively Show Scenarios of Genetic Bottlenecks and Clinical Response
Comparisons are made easier when scenarios share time axis and when shapes are reused, resizing where necessary. Adapted from Findlay et al. (2016).
(A) Complete clinical response.
(B) Bottlenecking, with new mutations appearing during treatment.
(C) Same as (B), but with only partial clinical response.
(D) Same as (B), but with no clinical response.
(E) Absence of bottlenecking or clinical response.
(F) A complex scenario.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

4. Figure 3
Graphical Strategies for Drawing Qualitative Clone Evolution Diagrams
(A) Avoid using a variety of shapes for the clone populations or gradients for shapes or backgrounds like in Findlay et al. (2016), Lundberg et al. (2014), and Jacoby et al. (2015). Do not indicate mutations using saturated dark colors (e.g., red) against a dark background, like in Humphries et al. (2013).
(B) Choose a template shape for all clone populations—tear droplets are flexible and can be lightly distorted without introducing uneven edges. Red stands out and is intuitively associated with negative outcome and is appropriate for clones that are resistant to treatment.
(C) Avoid using dark, saturated colors or a progression of dark-to-light colors, like in Yoshida et al. (2013) and Wang et al. (2014). Beware of using color combinations whose tone or hue may falsely suggest similarity between clones, and do not use different hues for highly related clones, like in Nik-Zainal et al. (2012) and Findlay et al. (2016). The ith mutation in gene X is labeled as X.i.
(D) Make use of qualitative Brewer palettes (Wong, 2010a), a progression of light-to-dark colors, a progression of similar hues to indicate similarity in mutation position, function, or relevance.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

5. Figure 4
Luminance of Colors Has a Powerful Effect on Their Visual Salience
Large luminance differences between adjacent colors or between the page, usually white, and colors at the border of shapes determine which elements draw the readers’ attention.
(A) Luminance values for each color are shown beside the phylogenetic tree. The bright yellow and rich magenta are more salient than the other colors.
(B) Adjusting luminance of colors from (A) helps reduce the differences in salience between unrelated clones but in some cases produces murky colors. Here, colors have been moved to better reflect the phylogeny of their corresponding clones.
(C) Greyscale Brewer palettes provide a good tone ramp.
(D) A color scheme that controls both luminance and chroma. No single color commands undue attention because differences in salience are subtle.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

6. Figure 5
Combining Quantitative Displays of Evolutionary Relationships and Clone Populations
(A) Clone populations, as measured for example by variant allele frequency (VAF), shown alongside phylogenetic tree. Successive generations are shown using thinner lines in the line plot.
(B) Population profiles for each generation shown next to the tree. Ancestor clone VAF profile is shown as a dotted line.
(C) Small multiples of clone population embedded in the tree. To more clearly depict trends, the clone populations can be shown with centered and stacked bars, and time within the small multiple plots can be made to flow left-to-right or downward.
(D) Emphasis on population rather than phylogenetic relationship, which can be subtly shown using spacing and alignment.
(E) Depending on the number of clones, time points, and available space, a vertical version of (D) may be preferred.
(F) A more complex plot with additional clones and time points. Population bars are distributed uniformly in the vertical direction, and the relationship to time is indicated by connecting lines to the time axis. Intervals of time can be subtly highlighted with a background fill.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions

7. Figure 6
Quantitative Clone Evolution Diagrams Combine Phylogenetic Relationships with Population Dynamics
Depending on the phylogenetic relationship, the order and alignment of shapes in quantitative evolution diagrams can be challenging to establish, particularly when the originating clone (light blue) continues to be present alongside its descendants.
(A) Seek a balance between simplicity of basic shapes like triangles and complex curves.
(B) Clone evolution for VAF profiles shown in Figure 4F and incorporating total tumor bulk either as a bar plot, showing both positive (shrinkage) and negative (growth) clinical response, or as a deformation of the diagram along the vertical axis.
(C) Evolution at different sites can be offset from the main diagram. Here, the main diagram is flipped vertically relative to (A) so that the orange clone is placed closer to its corresponding metastasis.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2016 Elsevier Inc. Terms and Conditions