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Poetry is just the evidence of life. If your life is burning well, poetry is just the ashLeonard Cohenburn somethingmore quotes

visualization: exciting

EMBO Practical Course: Bioinformatics and Genome Analysis, 5–17 June 2017.

science + genomics

What if we were to print what we sequence?

Expressing the amount of sequence in the human genome in terms of the number of printed pages has been done before. At the Broad Institute, all of the human reference genome is printed in bound volumes.

At our sequencing facility, we sequence about 1 terabases per day. This is equivalent to 167 diploid human genomes (167 × 6 gigabases). The sequencing is done using a pool of 13 Illumina HiSeq 2500 sequencers, of which about 50% are sequencing at any given time.

Martin Krzywinski @MKrzywinski
A single letter-size page (8.5" × 11") of 6pt Courier using 0.25 inch margins accomodates 18,126 bases on 114 lines. Shown here is a portion of sequence from human chromosome 1. (PDF)

This sequencing is extremely fast.

To understand just how fast this is, consider printing this amount of sequence using a modern office laser printer. Let's pick the HP P3015n which costs about $400—a cheap and fast network printer. It can print at about 40 pages per minute.

If we print the sequence at 6pt Courier using 0.25" margins, each 8.5" × 11" page will accomodate 18,126 bases. I chose this font size because it's reasonably legible. To print 1 terabases we need `10^12 / 18126 = 55.2` million pages.

If we print continuously at 40 pages per minute, we need `10^12 / (18126*40*1440) = 957.8` days.

If we had 958 printers working around the clock, we could print everything we sequence and not fall behind. This does not account for time required to replenish toner or paper.

what's cheaper, sequencing or printing?

It costs us about $12,000 to sequence a terabase in reagents. If we do it on a cost-recovery basis, it is about twice that, to include labor and storage. Let's say $25,000 per terabase.

Coincidentally, this is about $150 per 1× coverage of a diploid human genome. The cost of sequencing a single genome would be significantly higher because of overhead. To overcome gaps in coverage and to be sensitive to alleles in heterogenous samples, sequencing should be done to 30× or more. For example, we sequence cancer genomes at over 100×. For theory and review see Aspects of coverage in medical DNA sequencing by Wendl et al. and Sequencing depth and coverage: key considerations in genomic analyses by Sims et al.. (Thanks to Nicolas Robine for pointing out that redundant coverage should be mentioned here).

Printing is 44× more expensive than sequencing, per base: 25 n$ vs 1.1 μ$.

I should mention that the cost of analyzing the sequenced genome should be considered—this step is always the much more expensive one. In The $1,000 genome, the $100,000 analysis? Mardis asks "If our efforts to improve the human reference sequence quality, variation, and annotation are successful, how do we avoid the pitfall of having cheap human genome resequencing but complex and expensive manual analysis to make clinical sense out of the data?"

The cost of a single printed page (toner, power, etc) is about $0.02–0.05, depending on the printer. Let's be generous and say it's $0.02. To print 55.2 million pages would cost us $1.1M. This is about 44 times as expensive as sequencing.

Martin Krzywinski @MKrzywinski
To print what we sequence we would require 958 office laser printers (shown here as HP3015n) at a cost of $1,100,000 per day. (PDF)

Think about this. It's 44× more expensive to merely print a letter on a page than it is to determine it from the DNA of a cell. In other words, to go from the physical molecule to a bit state on a disk is much cheaper than from a bit state on a disk to a representation of the letter on a page.

Per base, our sequencing costs `$25000/10^12 = $25*10^-9`, or 25 nanodollars. At $0.02 and 18,126 bp per page, printing costs `0.02/18126 = $1.1*10^-6` or 1.1 microdollars.

If at this point you're thinking that printing isn't practical, the fact that the pages would weigh 248,000 kg and stack to 5.5 km should cinch the argument.

The capital cost of sequencing is, of course, much higher. The printers themselves would cost about $400,000 to purchase. The 6 sequencers, on the other hand, cost about $3,600,000.

sequencing is as fast as downloading

We sequence at a rate close to the average internet bandwidth available to the public.

At 3.86 Mb/s, we could download a terabase of compressed sequence in a day, assuming the sequence can be compressed by a factor of 3. This level of compression is reasonable—the current human assembly is 938 Mb zipped).

In other words, you would have to be downloading essentially continuously to keep up with our sequencing.


news + thoughts

Tabular Data

Tue 11-04-2017
Tabulating the number of objects in categories of interest dates back to the earliest records of commerce and population censuses.

After 30 columns, this is our first one without a single figure. Sometimes a table is all you need.

In this column, we discuss nominal categorical data, in which data points are assigned to categories in which there is no implied order. We introduce one-way and two-way tables and the `\chi^2` and Fisher's exact tests.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Tabular data. Nature Methods 14:329–330.

...more about the Points of Significance column

Happy 2017 `\pi` Day—Star Charts, Creatures Once Living and a Poem

Tue 14-03-2017

on a brim of echo,

capsized chamber
drawn into our constellation, and cooling.
—Paolo Marcazzan

Celebrate `\pi` Day (March 14th) with star chart of the digits. The charts draw 40,000 stars generated from the first 12 million digits.

Martin Krzywinski @MKrzywinski
12,000,000 digits of `\pi` interpreted as a star catalogue. (details)

The 80 constellations are extinct animals and plants. Here you'll find old friends and new stories. Read about how Desmodus is always trying to escape or how Megalodon terrorizes the poor Tecopa! Most constellations have a story.

Martin Krzywinski @MKrzywinski
Find friends and stories among the 80 constellations of extinct animals and plants. Oh look, a Dodo guardings his eggs! (details)

This year I collaborate with Paolo Marcazzan, a Canadian poet, who contributes a poem, Of Black Body, about space and things we might find and lose there.

Check out art from previous years: 2013 `\pi` Day and 2014 `\pi` Day, 2015 `\pi` Day and and 2016 `\pi` Day.

Data in New Dimensions: convergence of art, genomics and bioinformatics

Tue 07-03-2017

Art is science in love.
— E.F. Weisslitz

A behind-the-scenes look at the making of our stereoscopic images which were at display at the AGBT 2017 Conference in February. The art is a creative collaboration with Becton Dickinson and The Linus Group.

Its creation began with the concept of differences and my writeup of the creative and design process focuses on storytelling and how concept of differences is incorporated into the art.

Oh, and this might be a good time to pick up some red-blue 3D glasses.

BD Genomics 3D art exhibit - AGBT 2017 / Martin Krzywinski @MKrzywinski
A stereoscopic image and its interpretive panel of single-cell transcriptomes of blood cells: diseased versus healthy control.

Interpreting P values

Thu 02-03-2017
A P value measures a sample’s compatibility with a hypothesis, not the truth of the hypothesis.

This month we continue our discussion about `P` values and focus on the fact that `P` value is a probability statement about the observed sample in the context of a hypothesis, not about the hypothesis being tested.

Martin Krzywinski @MKrzywinski
Nature Methods Points of Significance column: Interpreting P values. (read)

Given that we are always interested in making inferences about hypotheses, we discuss how `P` values can be used to do this by way of the Benjamin-Berger bound, `\bar{B}` on the Bayes factor, `B`.

Heuristics such as these are valuable in helping to interpret `P` values, though we stress that `P` values vary from sample to sample and hence many sources of evidence need to be examined before drawing scientific conclusions.

Altman, N. & Krzywinski, M. (2017) Points of Significance: Interpreting P values. Nature Methods 14:213–214.

Background reading

Krzywinski, M. & Altman, N. (2017) Points of significance: P values and the search for significance. Nature Methods 14:3–4.

Krzywinski, M. & Altman, N. (2013) Points of significance: Significance, P values and t–tests. Nature Methods 10:1041–1042.

...more about the Points of Significance column

Snellen Charts—Typography to Really Look at

Sat 18-02-2017

Another collection of typographical posters. These ones really ask you to look.

Martin Krzywinski @MKrzywinski
Snellen charts designed using physical constants, Braille and elemental abundances in the universe and human body.

The charts show a variety of interesting symbols and operators found in science and math. The design is in the style of a Snellen chart and typset with the Rockwell font.