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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

Neural network primer

Mon 06-02-2023

Nature is often hidden, sometimes overcome, seldom extinguished. —Francis Bacon

In the first of a series of columns about neural networks, we introduce them with an intuitive approach that draws from our discussion about logistic regression.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Neural network primer. (read)

Simple neural networks are just a chain of linear regressions. And, although neural network models can get very complicated, their essence can be understood in terms of relatively basic principles.

We show how neural network components (neurons) can be arranged in the network and discuss the ideas of hidden layers. Using a simple data set we show how even a 3-neuron neural network can already model relatively complicated data patterns.

Derry, A., Krzywinski, M & Altman, N. (2023) Points of significance: Neural network primer. Nature Methods 20.

Background reading

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of significance: Logistic regression. Nature Methods 13:541–542.

Cell Genomics cover

Mon 16-01-2023

Our cover on the 11 January 2023 Cell Genomics issue depicts the process of determining the parent-of-origin using differential methylation of alleles at imprinted regions (iDMRs) is imagined as a circuit.

Designed in collaboration with with Carlos Urzua.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Our Cell Genomics cover depicts parent-of-origin assignment as a circuit (volume 3, issue 1, 11 January 2023). (more)

Akbari, V. et al. Parent-of-origin detection and chromosome-scale haplotyping using long-read DNA methylation sequencing and Strand-seq (2023) Cell Genomics 3(1).

Browse my gallery of cover designs.

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

Science Advances cover

Thu 05-01-2023

My cover design on the 6 January 2023 Science Advances issue depicts DNA sequencing read translation in high-dimensional space. The image showss 672 bases of sequencing barcodes generated by three different single-cell RNA sequencing platforms were encoded as oriented triangles on the faces of three 7-dimensional cubes.

More details about the design.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
My Science Advances cover that encodes sequence onto hypercubes (volume 9, issue 1, 6 January 2023). (more)

Kijima, Y. et al. A universal sequencing read interpreter (2023) Science Advances 9.

Browse my gallery of cover designs.

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

Regression modeling of time-to-event data with censoring

Mon 21-11-2022

If you sit on the sofa for your entire life, you’re running a higher risk of getting heart disease and cancer. —Alex Honnold, American rock climber

In a follow-up to our Survival analysis — time-to-event data and censoring article, we look at how regression can be used to account for additional risk factors in survival analysis.

We explore accelerated failure time regression (AFTR) and the Cox Proportional Hazards model (Cox PH).

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Nature Methods Points of Significance column: Regression modeling of time-to-event data with censoring. (read)

Dey, T., Lipsitz, S.R., Cooper, Z., Trinh, Q., Krzywinski, M & Altman, N. (2022) Points of significance: Regression modeling of time-to-event data with censoring. Nature Methods 19.

Music video for Max Cooper's Ascent

Tue 25-10-2022

My 5-dimensional animation sets the visual stage for Max Cooper's Ascent from the album Unspoken Words. I have previously collaborated with Max on telling a story about infinity for his Yearning for the Infinite album.

I provide a walkthrough the video, describe the animation system I created to generate the frames, and show you all the keyframes

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
Frame 4897 from the music video of Max Cooper's Asent.

The video recently premiered on YouTube.

Renders of the full scene are available as NFTs.

Gene Cultures exhibit — art at the MIT Museum

Tue 25-10-2022

I am more than my genome and my genome is more than me.

The MIT Museum reopened at its new location on 2nd October 2022. The new Gene Cultures exhibit featured my visualization of the human genome, which walks through the size and organization of the genome and some of the important structures.

Martin Krzywinski @MKrzywinski mkweb.bcgsc.ca
My art at the MIT Museum Gene Cultures exhibit tells shows the scale and structure of the human genome. Pay no attention to the pink chicken.

© 1999–2023 Martin Krzywinski | contact | Canada's Michael Smith Genome Sciences CentreBC Cancer Research CenterBC CancerPHSA