In 2001, the first human genome sequence was published. Now, just over 10 years later, we capable of sequencing a genome in just a few days. Massive parallel sequencing projects now make it possible to study the cancers of thousands of individuals. New data mining approaches are required to robustly interrogate the data for causal relationships among the inherently noisy biology. How does one identify genetic changes that are specific and causal to a disease within the rich variation that is either natural or merely correlated? The problem is one of finding a needle in a stack of needles. I will provide a non-specialist introduction to data mining methods and challenges in genomics, with a focus on the role visualization plays in the exploration of the underlying data.
The title of the talk was drawn from the paper
Gregory M. Cooper & Jay Shendure Needles in stacks of needles: finding disease-causal variants in a wealth of genomic data Nature Reviews Genetics 12, 628-640 (September 2011)
I will be posting a full list of references for the talk shortly.
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.
To achieve a `k` index for a movement you must perform `k` unbroken reps at `k`% 1RM.
The expected value for the `k` index is probably somewhere in the range of `k = 26` to `k=35`, with higher values progressively more difficult to achieve.
In my `k` index introduction article I provide detailed explanation, rep scheme table and WOD example.
The effect is intriguing and facetious—yes, those are real words.
But these are not: necronology, abobionalism, gabdologist, and nonerify.
These places only exist in the mind: Conchar and Pobacia, Hzuuland, New Kain, Rabibus and Megee Islands, Sentip and Sitina, Sinistan and Urzenia.
And these are the imaginary afflictions of the imagination: ictophobia, myconomascophobia, and talmatomania.
And these, of the body: ophalosis, icabulosis, mediatopathy and bellotalgia.
Want to name your baby? Or someone else's baby? Try Ginavietta Xilly Anganelel or Ferandulde Hommanloco Kictortick.
When taking new therapeutics, never mix salivac and labromine. And don't forget that abadarone is best taken on an empty stomach.
And nothing increases the chance of getting that grant funded than proposing the study of a new –ome! We really need someone to looking into the femome and manome.