If your photos aren’t good enough, then you’re not close enough
— Robert Capa
Papillary thyroid carcinoma (PTC) cells, even though malignant, are still genetically programmed to try to be thyroid follicles and may retain their follicular growth pattern, which appear as circles on cross section. Two diagnostic features of papillary thyroid carcinoma are nuclear clearing and intranuclear cytoplasmic inclusions. The black-and-white image is an artistic treatment of a PTC microscopy image (40×) from one of the Personalized Oncogenomics Program study participants at the BC Cancer Research Center. Superimposed is a Circos plot of 17 genomic fusions involving 17 chromosomes identified in the sample by whole-genome sequencing. Showing through the Circos plot is an enhanced color version of the microscopy image. The original image is from Application of genomics to identify therapeutic targets in recurrent pediatric papillary thyroid carcinoma by Ronsley et al. in the April 2018 issue.
The theme of the April issue of Molecular Case Studies is precision oncogenomics. We have three papers in the issue based on work done in our Personalized Oncogenomics Program (POG).
...this special issue provide[s] a glimpse into current cancer precision medicine efforts, reflecting only a microcosm of ... genomics in this bustling space of clinical translation.
John C. Carpten & Elaine R. Mardis
The era of precision oncogenomics
Mol. Case Stud. (2018) 4(2).
I've previously created art based on POG data—posters to celebrate the program's 5-year anniversary.
The covers of Molecular Case Studies typically show microscopy images, with some shown in a more abstract fashion. There's also the occasional Circos plot.
I've previously taken a more fine-art approach to cover design, such for those of Nature, Genome Research and Trends in Genetics. I've used microscopy images to create a cover for PNAS—the one that made biology look like astrophysics—and thought that this is kind of material I'd start with for the MCS cover.
When I look at these kind of images, I have basically no idea what I'm looking at. Sure, I know this is life at tiny scale but I am not a pathologist. This helps me greatly.
Instead, I see color, shapes, and contrast. I hunt for patterns that would make for an interesting visual, without necessarily trying to communicate any of the science behind that—the paper does a much better job at this than I ever could. It's largely a process driven by intuition and my desire to see distinct visual patterns at different length scales with some symmetry, ideally broken in a pleasing way. Vague, I know.
Images of different regions of the same slide, at the same magnification, can have very different levels of visual engagement (for the non-specialist). Just compare the two images below.
The slide on the left really caught my eye. It had the right proportion of tiny, small, medium and large things.
The black-and-white version was obtained by solarizing the image. There are both color and black-and-white options for solarization, a method in which various tones of the image are remapped in brightness.
And here's the first black-and-white take.
This looked good but a bit dark. I handled this by lightening the tone, differently depending on the element in the image. I also wanted to bring out more details in the internal structure of the cells. This was achieved by applying an otherwise aggressive sharpening mask.
I was quite happy with this result. The combination of solarization and sharpening created a large variety of patterns inside the cells. My brain fought hard to see faces in them.
Because I had slides at different magnifications, I created a design in which three slides at 10, 20 and 40 × were composited together so that from left to right the magnification increased across the image. The effect is subtle—you can easily miss it, which is the point.
I had pretty high hopes for these black-and-white versions. Previous covers in MCS have been colorful, though, so I thought to provide a color option.
For the color version, I wanted to give the colors more punch. For sure.
I also wanted to emphasize the details, like for the black-and-white image.
The first process step of the color slide was done using 5 Nik filters, applied in succession: dark contrast, tonal contrast, sunlight, polarization and detail extractor. The effects of the stack of these filters is shown on the original image below. The whole image is shown and in each strip the filters are stacked.
Here's the full image with the 5 Nik filters applied.
Not there yet, though. I added more sharpening (more than I've ever used before, so I felt a little weird, but got over it quickly). The colors were punched up too—I wanted more contrast between the blue and red areas and transform the reds a little into oranges.
If it looks like the blue areas are popping out of the image, that's the effect of the emboss filter.
The editors asked me to encorporate a Circos image in the final design. This was tricky—I had spent a lot of time up to now fiddling with extracting patterns and textures from the images.
Something as geometrical and rational as a data graphic would alter the personality of the design. But, the goal of artistic collaboration is always to find a way, so I took some gene fusions that were found in the sample with our structural variant pipeline and created a bare-bones Circos image out of them.
This was then superimposed on the image and emphasized by using the color design inside the circle and black-and-white design outside.
It's always fun to invert images and see what happens.
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.
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.
Lever, J., Krzywinski, M. & Altman, N. (2016) Points of significance: Logistic regression. Nature Methods 13:541–542.
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.
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.
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.
Kijima, Y. et al. A universal sequencing read interpreter (2023) Science Advances 9.
Browse my gallery of cover designs.
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).
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.
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
The video recently premiered on YouTube.
Renders of the full scene are available as NFTs.
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.