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Distractions and amusements, with a sandwich and coffee.

Without an after or a when.
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• can you hear the rain?
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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.

*You can look back there to explain things,
but the explanation disappears.
You'll never find it there.
Things are not explained by the past.
They're explained by what happens now.
—Alan Watts*

A Markov chain is a probabilistic model that is used to model how a system changes over time as a series of transitions between states. Each transition is assigned a probability that defines the chance of the system changing from one state to another.

Together with the states, these transitions probabilities define a stochastic model with the Markov property: transition probabilities only depend on the current state—the future is independent of the past if the present is known.

Once the transition probabilities are defined in matrix form, it is easy to predict the distribution of future states of the system. We cover concepts of aperiodicity, irreducibility, limiting and stationary distributions and absorption.

This column is the first part of a series and pairs particularly well with Alan Watts and Blond:ish.

Grewal, J., Krzywinski, M. & Altman, N. (2019) Points of significance: Markov Chains. *Nature Methods* **16**:663–664.

*Places to go and nobody to see.*

Exquisitely detailed maps of places on the Moon, comets and asteroids in the Solar System and stars, deep-sky objects and exoplanets in the northern and southern sky. All maps are zoomable.

Quantile regression explores the effect of one or more predictors on quantiles of the response. It can answer questions such as "What is the weight of 90% of individuals of a given height?"

Unlike in traditional mean regression methods, no assumptions about the distribution of the response are required, which makes it practical, robust and amenable to skewed distributions.

Quantile regression is also very useful when extremes are interesting or when the response variance varies with the predictors.

Das, K., Krzywinski, M. & Altman, N. (2019) Points of significance: Quantile regression. *Nature Methods* **16**:451–452.

Altman, N. & Krzywinski, M. (2015) Points of significance: Simple linear regression. *Nature Methods* **12**:999–1000.

Outliers can degrade the fit of linear regression models when the estimation is performed using the ordinary least squares. The impact of outliers can be mitigated with methods that provide robust inference and greater reliability in the presence of anomalous values.

We discuss MM-estimation and show how it can be used to keep your fitting sane and reliable.

Greco, L., Luta, G., Krzywinski, M. & Altman, N. (2019) Points of significance: Analyzing outliers: Robust methods to the rescue. *Nature Methods* **16**:275–276.

Altman, N. & Krzywinski, M. (2016) Points of significance: Analyzing outliers: Influential or nuisance. Nature Methods 13:281–282.

Two-level factorial experiments, in which all combinations of multiple factor levels are used, efficiently estimate factor effects and detect interactions—desirable statistical qualities that can provide deep insight into a system.

They offer two benefits over the widely used one-factor-at-a-time (OFAT) experiments: efficiency and ability to detect interactions.

Since the number of factor combinations can quickly increase, one approach is to model only some of the factorial effects using empirically-validated assumptions of effect sparsity and effect hierarchy. Effect sparsity tells us that in factorial experiments most of the factorial terms are likely to be unimportant. Effect hierarchy tells us that low-order terms (e.g. main effects) tend to be larger than higher-order terms (e.g. two-factor or three-factor interactions).

Smucker, B., Krzywinski, M. & Altman, N. (2019) Points of significance: Two-level factorial experiments *Nature Methods* **16**:211–212.

Krzywinski, M. & Altman, N. (2014) Points of significance: Designing comparative experiments.. Nature Methods 11:597–598.