Art of the Personalized Oncogenomics Program
In research the horizon recedes as we advance, and is no nearer at sixty than it was at twenty. As the power of endurance weakens with age, the urgency of the pursuit grows more intense ... And research is always incomplete.
— Mark Pattison (Isaac Casaubon)
contents
The legend can be printed at 4" × 6". The bitmap resolution is 600 dpi.
For every case, we sequence the DNA to study the genome structure and the RNA to discover which genes are expressed and to what extent. The analysis is quite complex and brings together many steps: sequence alignment, structural variation detection, expression profiling, pathway analysis and so on. Every case is "summarized" by a lengthy report, such as the one below, which can run to over 40 pages.
One of the goals of the 5-year anniversary art was to represent the cases in a way to clearly show their number, classification as well as diversity. There are many metrics that can be used and I decided to choose the case's correlation to other cancer types.
correlation to TCGA cancer database
For every POG case, the gene expression of 1,744 key genes is compared to that of 1,000's of cases in the TCGA database of cancer samples. For a given cancer type in the TCGA database (e.g. BRCA), we visualize the correlations using box plots. The box plot is ideal for showing the distribution of values in a sample.
The 10 largest Spearman correlation coefficients for the case shown above are
case corr type tissue ----------------------------------------------- POG661 0.436 BRCA Breast POG661 0.371 PRAD Urologic POG661 0.295 OV Gynecologic POG661 0.257 UCEC Gynecologic POG661 0.244 LUAD Thoracic POG661 0.235 CESC_CAD Gynecologic POG661 0.225 MB_Adult Central Nervous System POG661 0.222 KICH Urologic POG661 0.219 THCA Endocrine POG661 0.208 UCS Gynecologic
In the figure below I show how the final encoding of the correlations is done. First, the top three correlations are taken—using more generates a busy look and diminishes visual impact. The correlations are encoded as concentric rings.
Because in most cases the differences in the top 3 correlations are relatively small, differences are emphasized by non-linearly scaling the encoding (the correlations are first scaled `r^3`).
The type face is Proxima Nova. The colors for each tissue source are
Gastrointestinal ● 234,62,144
Breast ● 237,75,51
Thoracic ● 242,130,56
Gynecologic ● 253,188,61
Soft tissue ● 244,217,59
Skin ● 193,216,51
Urologic ● 114,197,49
Hematologic ● 29,166,68
Head and neck ● 43,168,224
Endocrine ● 71,82,178
Central nervous system ● 127,65,146
Other ● 150,150,150
Convolutional neural networks
Nature uses only the longest threads to weave her patterns, so that each small piece of her fabric reveals the organization of the entire tapestry. – Richard Feynman
Following up on our Neural network primer column, this month we explore a different kind of network architecture: a convolutional network.
The convolutional network replaces the hidden layer of a fully connected network (FCN) with one or more filters (a kind of neuron that looks at the input within a narrow window).
Even through convolutional networks have far fewer neurons that an FCN, they can perform substantially better for certain kinds of problems, such as sequence motif detection.
Derry, A., Krzywinski, M & Altman, N. (2023) Points of significance: Convolutional neural networks. Nature Methods 20:.
Background reading
Derry, A., Krzywinski, M. & Altman, N. (2023) Points of significance: Neural network primer. Nature Methods 20:165–167.
Lever, J., Krzywinski, M. & Altman, N. (2016) Points of significance: Logistic regression. Nature Methods 13:541–542.
Neural network primer
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 20:165–167.
Background reading
Lever, J., Krzywinski, M. & Altman, N. (2016) Points of significance: Logistic regression. Nature Methods 13:541–542.
Cell Genomics cover
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.
Science Advances cover
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.
Regression modeling of time-to-event data with censoring
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 19:1513–1515.
Music video for Max Cooper's Ascent
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.