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Distractions and amusements, with a sandwich and coffee.

Without an after or a when.
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It is said that for money you can have everything, but you cannot. You can buy food, but not appetite; medicine, but not health; knowledge, but not wisdom; glitter, but not beauty; fun, but not joy; acquaintances, but not friends; servants, but not faithfulness; leisure, but not peace. You can have the husk of everything for money, but not the kernel.

— Arne Garborg

I have recently had the opportunity to contribute to The Objects that Power the Global Economy, a book by Quartz.

The book is about objects that have impact on our world and our lives. "Each chapter of this book examines an object that is driving radical change in the global economy: how we communicate, what we eat, the way we spend our money. The stories are told through global reporting, original photography and illustration by award-winning artists, contributions from business visionaries, data visualization, and interactive features." (Quartz).

My illustration is of the human genome with a focus on the genes that have been implicated in disease.

We have about 30,000 genes and about half of these play some role in disease.

You can peruse what we know about the connection between genetics and illness at the Online Mendelean Inheritance of Man database. For example, a cursory search for "cancer" results in over 3,500 entries.

It's important to realize that these aren't genes that *cause* disease—its misregulation and mutations in them that are associated with disease (causality is complicated).

The illustration shows the genome as a single line, wound in an Archimedean spiral. Chromosomes 1–22 are shown binned into about 10,000 regions along the spiral. Regions that have genes associated with disease are marked with dots—the size of the dot shows how many such genes are found. Each region corresponds to about 286,000 bases.

We see that in about 73% of the 286 kb regions, there are no genes. In about 18% we see a single gene and in roughly 10% two genes or more.

regions genes 7,321 0 1,812 1 556 2 221 3 85 4 93 5+

Winding the genome up in a spiral creates a compact representation. Squishing a line onto a page can be tricky.

Luckily, space filling curves like the Hilbert curve are very efficient at doing this. I've previously shown the genome along a Hilbert curve for a Scientific American Graphic Science page.

I show several versions of the illustrations below. In the book, the image is printed on a black background.

Just in time for the season, I've simulated a snow-pile of snowflakes based on the Gravner-Griffeath model.

Gravner, J. & Griffeath, D. (2007) Modeling Snow Crystal Growth II: A mesoscopic lattice map with plausible dynamics.

My illustration of the location of genes in the human genome that are implicated in disease appears in The Objects that Power the Global Economy, a book by Quartz.

We introduce two common ensemble methods: bagging and random forests. Both of these methods repeat a statistical analysis on a bootstrap sample to improve the accuracy of the predictor. Our column shows these methods as applied to Classification and Regression Trees.

For example, we can sample the space of values more finely when using bagging with regression trees because each sample has potentially different boundaries at which the tree splits.

Random forests generate a large number of trees by not only generating bootstrap samples but also randomly choosing which predictor variables are considered at each split in the tree.

Krzywinski, M. & Altman, N. (2017) Points of Significance: Ensemble methods: bagging and random forests. *Nature Methods* **14**:933–934.

Krzywinski, M. & Altman, N. (2017) Points of Significance: Classification and regression trees. *Nature Methods* **14**:757–758.

Decision trees classify data by splitting it along the predictor axes into partitions with homogeneous values of the dependent variable. Unlike logistic or linear regression, CART does not develop a prediction equation. Instead, data are predicted by a series of binary decisions based on the boundaries of the splits. Decision trees are very effective and the resulting rules are readily interpreted.

Trees can be built using different metrics that measure how well the splits divide up the data classes: Gini index, entropy or misclassification error.

When the predictor variable is quantitative and not categorical, regression trees are used. Here, the data are still split but now the predictor variable is estimated by the average within the split boundaries. Tree growth can be controlled using the complexity parameter, a measure of the relative improvement of each new split.

Individual trees can be very sensitive to minor changes in the data and even better prediction can be achieved by exploiting this variability. Using ensemble methods, we can grow multiple trees from the same data.

Krzywinski, M. & Altman, N. (2017) Points of Significance: Classification and regression trees. *Nature Methods* **14**:757–758.

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

Altman, N. & Krzywinski, M. (2015) Points of Significance: Multiple Linear Regression *Nature Methods* **12**:1103-1104.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Classifier evaluation. *Nature Methods* **13**:603-604.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Model Selection and Overfitting. *Nature Methods* **13**:703-704.

Lever, J., Krzywinski, M. & Altman, N. (2016) Points of Significance: Regularization. *Nature Methods* **13**:803-804.

The artwork was created in collaboration with my colleagues at the Genome Sciences Center to celebrate the 5 year anniversary of the Personalized Oncogenomics Program (POG).

The Personal Oncogenomics Program (POG) is a collaborative research study including many BC Cancer Agency oncologists, pathologists and other clinicians along with Canada's Michael Smith Genome Sciences Centre with support from BC Cancer Foundation.

The aim of the program is to sequence, analyze and compare the genome of each patient's cancer—the entire DNA and RNA inside tumor cells— in order to understand what is enabling it to identify less toxic and more effective treatment options.

Principal component analysis (PCA) simplifies the complexity in high-dimensional data by reducing its number of dimensions.

To retain trend and patterns in the reduced representation, PCA finds linear combinations of canonical dimensions that maximize the variance of the projection of the data.

PCA is helpful in visualizing high-dimensional data and scatter plots based on 2-dimensional PCA can reveal clusters.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Principal component analysis. *Nature Methods* **14**:641–642.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Clustering. *Nature Methods* **14**:545–546.