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A phylogenetic tree of 235 million sequences in full bloom.

EMBO Journal 2011 Cover Contest

1 · EMBO Journal — best scientific cover of 2010

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Four genomes — The illustration, originally part of a poster, shows syntenic relationships between human, chimpanzee, mouse and zebrafish genomes. Curved links encode sequence similarity and outer data tracks represent consensus similarity statistics and orthologous genes. The cover image shows a detail of a visualization prepared with the free genome comparison tool, Circos.

For its 6 May 2009 issue, the EMBO Journal selected my submission of a large Circos figure for its cover. At the time, front page exposure of this sort has made Circos a very popular tool for visualization in genomics, and in particular, in cancer research where there is a need to illustrate differences between genomes.

Below I describe a couple of subsequent submissions for the EMBO Journal 2011 Cover Contest — a scientific entry and a non-scientific entry.

For the EMBO Journal 2011 Cover Contest, I prepared two entries, one for the scientific category and one for the non-scientific category.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The non-scientific entry is abstract photo of fiber optics. The scientific entry was an information graphic showing a hive panel of genomic annotations in human, mouse and dog genomes. The hive panel is based on the use of the newly introduced hive plot.

2 · About the EMBO Journal cover contest

The EMBO Journal non-scientific cover prize is awarded for the most interesting and beautiful image made outside the lab. Contestants may submit, for example, photos or artistic impressions of wildlife animals, plants or landscapes. Particularly welcome will also be hand or computer-generated paintings or drawings (or photographs of other works of art) related to a biological or molecular biological topic.

The EMBO Journal scientific cover prize is awarded for the most captivating and thought-provoking contribution depicting a piece of molecular biology research. Entries can include light or electron micrographs, 3D reconstructions or models of biological specimen or molecules, spectacular artefacts collected in the lab, original new views of lab equipment (but not of colleagues!), or other research-based images to be of interest to molecular biologists.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Examples of scientific cover image winners from previous years. My Circos image (top left) won the 2010 scientfic image cover category.

3 · Scientific image entry — a hive panel

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Final EMBO Journal cover submissions. (More about hive plots.)

4 · Current state of network visualization

A large number of layout algorithms already exist to attempt to visualize networks. In an attempt to create attractive layouts, node and edge positions are optimized to minimize some fitness function, such as overlap or force (if edges are treated as springs). Unfortunately, as a result it is impossible to relate the position of a node (or the distance between any two nodes in the layout) to their connected neighbourhood in the network. This particularly holds for large networks, where nodes and edge overlap in the layout is unavoidable.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Hairballs are irrational network visualizations. Shown here are 8 different layouts of the same network — it is impossible to identify that these images correspond to the same network. More importantly, it is very difficult to extract meaningful and quantitative information from these layouts.

5 · The hive plot

The hive plot is a rational approach to visualizing networks. It is designed to complement (at times, replace) the network hairball.

5.1 · Hive plots for networks

In a hive plot, network nodes are assigned to and placed on axes using rational rules. These rules typically are a function of local network structure around the node (connectivity, density, centrality, etc). The resulting plot is interpretable.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
In a hive plot, nodes in a network are assigned and placed on axes using properties of the node and its relationship to its neighbours. The resulting layout is rational and easily interpreted, because the rules are based on meaningful quantities. (Hive plots rationalize network visualization.)

5.2 · Hive plots for ratios

The hive plot can be applied to visualize a large number of ratios between three or more scales.

Instead of network edges, the lines in a hive plot now correspond to an (x,y) data pair, which can be interpreted as a ratio (x/y). This approach is particularly effective when lines are drawn as ribbons, which are then stacked. This is shown in the figure below.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A hive plot can be used to visualize ratios by rendering individual ratios as stacked ribbons. The result is the circular equivalent of a stacked bar plot

The resulting visualization bears resemblance to a stacked bar plot. The circular layout grants the advantage of being able to instantly compare all pair-wise comparisons between the axes (when three axes are used). This layout also gives the image a compare compact feel and is particularly suitable for tiling.

In the examples below, a 3-axis hive plot is shown with 8 ratios between each axis. The ratios are independent, in the sense that corresponding ribbons (e.g. blue) may have different thickness on either side of an axis. For example, if x:z = 2:3 and x:y = 1:3 then the ribbon on the left of the x axis will be twice as thick as on the right (see black arrow in figure below).

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
In a dual scale hive plot, each axis supports two groups of independent ribbons. Axes can be hidden (A), shown (B), or split by various amounts (C 20deg, D 30deg, E 40deg, F 60deg) to explicitly show the transition between ribbons on either side of the axis. Download high-resolution panels A B C D E F

The axes in a hive plot can be arranged arbitrarily. In the figure above panels A and B show 24 ratios — 8 each between x/y, x/z, and y/x axes. In panels C-F each axis is split to create a single 6-axis plot from a dual 3-axis plot. The split axes reveal the transition between ribbons from the left and right sides.

The dual 3-axis plot appears more stylized and mathematical, whereas the single 6-axis plot is softer and organic. As the axis split distance is increased, the plots begin to look like surface density maps, which to some degree occludes the relationships between the ratio ribbons.

5.3 · Comparing genome annotations

For each of human (hg18), mouse (mm8) and dog (canfam2) genome assemblies, UCSC annotations, available for each genome from the table browser, were used to hierarchically organize each base in the assembly using the following criteria: gene, repeat and gene+repeat. For each of these, bases were further categorized as conserved or not.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Each base in the genome assembly was assigned to one of eight disjoint categories.

By exhaustively intersecting each of the annotation regions, the assembly was divided into disjoint segments, each with its annotation states. For example, below are a few adjacent regions from hg18 chr1 (a assembly, r repeat, c-cf conserved with dog, c-mm conserved with mouse).

...
hg 1 120,942,663 120,945,658 2,996 a r
hg 1 120,945,659 120,945,665     7 a
hg 1 120,945,666 120,947,239 1,574 a c-cf c-mm
hg 1 120,947,240 120,947,243     4 a c-cf c-mm r
hg 1 120,947,244 120,947,268    25 a c-mm r
hg 1 120,947,269 120,950,367 3,099 a r
hg 1 120,950,368 120,950,386    19 a
...

Next, the total size of regions for each combination of annotation was calculated for each pairwise combination of genomes. The second genome in the pair dictates which conservation is used. For example, for the human-mouse pair, the relative fractions of the human genome that fall into each of the categories are

hg mm a        1,839,255,050 0.643542044483869
hg mm a,c-mm     757,027,260 0.264878365091574
hg mm a,r        206,719,589 0.0723296896425132
hg mm a,c-mm,r    42,358,464 0.0148209203088807
hg mm a,g          8,139,587 0.00284798264342638
hg mm a,c-mm,g     4,435,658 0.0015520046651231
hg mm a,g,r           48,994 1.71426463814481e-05
hg mm a,c-mm,g,r      33,869 1.18505182327074e-05

thus categorizing all the 2.86 Gb of the assembled human genome. The corresponding ratios for the mouse genome are

mm hg a          1,388,193,028 0.544355712823795
mm hg a,c-hg       892,892,218 0.350132128602082
mm hg a,r          196,173,508 0.0769260237089193
mm hg a,c-hg,r      62,305,053 0.0244318411447455
mm hg a,g            6,377,904 0.00250098394691097
mm hg a,c-hg,g       4,076,727 0.00159861747416369
mm hg a,g,r             81,889 3.21113447973805e-05
mm hg a,c-hg,g,r        57,585 2.2580954586784e-05

Using these two lists, all the ratios between the human and mouse axes can be determined. For example, for the conserved/gene/non-repeat regions the ratio of human:mouse is 0.00155:0.00160 (lines are bolded above). The corresponding ribbon for this ratio is shown below.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The ratio of conserved gene regions not in repeats between human and mouse genomes.

Category assignment into repeat, gene and conserved region was parametrized into three ranges for each criteria. These values were selected heuristically, to obtain a reasonable sample for each combination.

  • gene g1 <4kb, g2 4kb-22kb, g3 >22kb
  • repeat r1 simple, r2 LTR, r3 LINE/SINE
  • conservation c1 <45%, c2 45%-58%, c3 >58%

Given 3 parameters for each of the categories, the full comparison is represented by 27 hive plots. These plots are arranged on the cover as follows

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The ratio of conserved gene regions not in repeats between human and mouse genomes.

The scale of the axes was logarithmic to maintain visibility of all categories.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
The ratio of conserved gene regions not in repeats between human and mouse genomes.

6 · Non-scientific image entry

My 2011 non-scientific fiber optic entry received an honorouable mention. Oh well, we can't always have nice things.

By compositing images shot across time into a single frame, I show the passage of time in a still photograph.
I am the former owner of the world's most popular rat. See the photos and be adjacent to fame.

6.1 · Fibre optic lamp photos

Some time ago, I photographed fiber optic strands. These worked out well. I had not done anything with these images, and thought they would make a competitive entry into the cover contest.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
My first attempt at photographing fiber optic lamp strands. These images were bundled into a set called Diving Horror, because of their likeness to creepy tentacles of creatures of the deep.

I revisited the fiber optic lamp with a higher resolution camera (Canon 5D — original images were from a Canon 20D) and a dedicated macro lens (Sigma 150mm f2.8 EX APO DG HSM Macro) (original images were shot with the Canon EF 24-70L).

From these new images, shown below, I created five EMBO Journal cover submissions.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Second attempt at photographing fiber optic lamp strands.

The submissions would render on the cover as shown below.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2011 EMBO Cover contest submission — macro photograph of fiber optic lamp strands.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2011 EMBO Cover contest submission — macro photograph of fiber optic lamp strands.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2011 EMBO Cover contest submission — macro photograph of fiber optic lamp strands.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2011 EMBO Cover contest submission — macro photograph of fiber optic lamp strands.
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2011 EMBO Cover contest submission — macro photograph of fiber optic lamp strands.
news + thoughts

Nature Biotechnology cover

Thu 23-04-2026

My cover design on the 7 April 2026 Nature Biotechnology issue shows the dendrogram that represents a cluster of uniquely expressed (or downregulated) genes in human naive stem cells induced from such cells. Within each dendrogram block, the genomic barcode sequence (sampled from Supplementary Table 1) is depicted with a Code 39 barcode. The highlighted barcode is one of those used for cell isolation.

Ishiguro S. et al. A multi-kingdom genetic barcoding system for precise clone isolation (2026) Nature Biotechnology 44:616–629.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
My Nature Biotechnology phylogenetic tree cover (volume 44, issue 4, 7 April 2026). (more)

Browse my gallery of cover designs.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
A catalogue of my journal and magazine cover designs. (more)

Happy 2026 π Day—
Art for the 5%

Fri 13-03-2026

Celebrate π Day (March 14th) and enjoy the art — but only if you're part of the 5%.

Go ahead, see what you can't see.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
2026 π DAY | Art for the 5%. Shown in the style of Ishihara color test plates, the art is visible only to those with colour blindness. (details)

Ishihara's Tests for Colour Deficiency

Sun 08-03-2026

Authentic and accurate images of Ishihara's test plates photographed (and lovingly color-corrected) from the 38-plate Ishihara's Tests for Colour Deficiency.

I also provide the position, size, and color of each circle on each test plate.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
ISHIHARA'S TEST PLATE 6 | This plate is part of the set of transformation plates. If you see 5, you're ok. If you see 2, you're not. (details)
Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
ISHIHARA'S TEST PLATE 18 | This plate is part of the set of mysterious hidden plates. If you don't see anything, you're ok. If you see 5, you're not. (details)

Symmetric alternatives to the ordinary least squares regression

Wed 23-07-2025

What immortal hand or eye, could frame thy fearful symmetry? — William Blake, "The Tyger"

This month, we look at symmetric regression, which, unlike simple linear regression, it is reversible — remaining unaltered when the variables are swapped.

Simple linear regression can summarize the linear relationship between two variables `X` and `Y` — for example, when `Y` is considered the response (dependent) and `X` the predictor (independent) variable.

However, there are times when we are not interested (or able) to distinguish between dependent and independent variables — either because they have the same importance or the same role. This is where symmetric regression can help.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Symmetric alternatives to the ordinary least squares regression. Geometry of quantities minimized in OLS and symmetric regression. OLS minimizes `\Sigma e_y^2` in `Y` ~ `X` and `\Sigma e_x^2` `X` ~ `Y`. Pythagorean regression minimizes AB (magenta). Geometric means regression (GMR) minimizes area of ABP (orange). Orthogonal regression (OR) minimizes HP (blue). (read)

Luca Greco, George Luta, Martin Krzywinski & Naomi Altman (2025) Points of significance: Symmetric alternatives to the ordinary least squares regression. Nat. Methods 22:1610–1612.

Beyond Belief Campaign BRCA Art

Wed 11-06-2025

Fuelled by philanthropy, findings into the workings of BRCA1 and BRCA2 genes have led to groundbreaking research and lifesaving innovations to care for families facing cancer.

This set of 100 one-of-a-kind prints explore the structure of these genes. Each artwork is unique — if you put them all together, you get the full sequence of the BRCA1 and BRCA2 proteins.

Propensity score weighting

Mon 17-03-2025

The needs of the many outweigh the needs of the few. —Mr. Spock (Star Trek II)

This month, we explore a related and powerful technique to address bias: propensity score weighting (PSW), which applies weights to each subject instead of matching (or discarding) them.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Propensity score weighting. (read)

Kurz, C.F., Krzywinski, M. & Altman, N. (2025) Points of significance: Propensity score weighting. Nat. Methods 22:638–640.

Martin Krzywinski | contact | Canada's Michael Smith Genome Sciences CentrePHSA
Google whack “vicissitudinal corporealization”
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