# Big data visualization using HiGlass

• 05 Nov 2018
• |
• higlass
• python
• |

The past decade has seen tremendous advances in the field of data visualization. Libraries such as D3.js have made it not only possible but easy to create complex, informative and beautiful visualizations. Vega and vega lite introduced declarative specifications for describing both how data should be plotted and how the user should interact with it. A cadre of other libraries and services let people create interactive plots that they can share in web browsers.

Most of these tools and libraries, however, have one glaring limitation. They require loading and operating on the the entire dataset. This precludes their use with data too large to fit into memory or to render at once. Even with smaller datasets, issues such as occlusion and overplotting can make it difficult to explore and analyze data. This need not be the case. We already have techniques that allow us to break down large datasets into smaller, digestible chunks which can be displayed without overwhelming the rendering library or viewer.

## Inspired by maps

Online maps, for example, are a de-facto visualization of terabyte-scale datasets. They rely on a very simple principle: only render what is relevant at a given scale and location. Modern “slippy maps” partition data into tiles which are indexed using three integers:

• z - the zoom level (scale) at which we are viewing the map
• x - the x position of the “tile”
• y - the y position of the “tile”

In a typical map, there are 19 zoom levels. The lowest, 0, contains a single tile which covers the entire world. The next zoom level, 1, contains 4 tiles. Each one a quarter of the area of the previous one. The highest zoom level, 19, contains 4 ^ 19 tiles. Which tiles are loaded at any given time depends on the scale and the location of the map. Typically, only a handful of tiles are loaded at any given time. By limiting the amount of data contained in each tile and the number of tiles visible at any given time, we effectively limit the amount of data that needs to be loaded and rendered.

Online maps are rendered by retrieving and stitching together small images called *tiles*. The view on the right shows the tiles that make up the zoomable map on the left.

This technique makes it possible to access terabyte-scale datasets on hardware as basic as a mobile phone. Can we learn from this approach and apply it to other types of data? We certainly can. It just requires defining and implementing two operations on a set of data:

1. Downsampling
2. Slicing

With these two operations, we can create maps-like displays for any two (or one) dimensional data, regardless of its size.

## Hi-C contact matrices

Figure 2: A Hi-C contact matrix shown at three different scales highlighting chromosomes (top), compartments (middle) and TADs and loops (bottom).

Until recently, there were few datasets that were too large to display at once, worth viewing in the their entirety and relevant at multiple scales. Maps, of course, are one. Genomes are another. The human genome is over 3 billion base pairs long. If stretched end to end it would span nearly two meters. In each cell of the human body, it is exquisitely packed into a nucleus that is roughly 10 micrometers across (depending on the cell). That is the equivalent of packing a 50 mile long string into a volume roughly the size of a basketball. Needless to say, it’s a snug fit.

The question that, through a long and winding journey, led to this blog post is “what is the shape of DNA inside the nucleus of a cell?”. To answer this question, a number of research groups perform what are known as Hi-C assays. These assays survey which parts of the genome are in contact with each other. The results come in the form of a matrix. On one axis is the genome and on the other, the same genome. Each cell contains a count of how many times the assay “caught” those two portions of the genome in close proximity to each other. To make things statistically simpler, each “portion” of the genome is a segment one thousand nucleotides in length. So in the end, we end up with a 3 million x 3 million matrix describing how the DNA is folded within the nucleus. If you took this matrix and plotted it, you would see chromosomes, compartments and TADs, all at different scales. But how does one plot a 3 million by 3 million matrix?

## Downsampling and slicing

With current technology, there is simply no way to plot a 3 million x 3 million matrix at once. To do so would require an monitor the size of the empire state building. But we don’t have to plot it once. We can be like maps and only show what is relevant given the scale and location. As we mentioned earlier, this requires the ability to downsample and slice. When zoomed out, we want to see a downsampled data such that each cell represents more than the original one thousand base pairs. When zoomed in, we want to see the subset of data that is visible in the viewport.

With a matrix, these operations are simple. Downsampling can be done by summing adjacent cells of the matrix:

>>> import numpy as np
>>> a = np.array([[1,2,3,4],
[5,6,7,8],
[9,10,11,12],
[13,14,15,16]])
>>> b = np.nansum(a.reshape((a.shape[0],-1,2)), axis=2)
>>> b
array([[ 3,  7],
[11, 15],
[19, 23],
[27, 31]])
>>> c = np.nansum(b.T.reshape(b.shape[1], -1, 2), axis=2).T
>>> c
array([[14, 22],
[46, 54]])


And slicing can be done by, well, slicing the matrix:

>>> a[2:4,2:4]
array([[11, 12],
[15, 16]])


## Tiling

With downsampling and slicing functions, we’re ready to generate tiles. The zoom level of each tile corresponds to the level of downsampling of the original data. If we follow the example of online maps, the lowest zoom level, 0, will contain the entire matrix. The highest zoom level, 14, in our case will contain the original data. All the zoom levels in between will contain data at resolutions which are powers of two multiples of the original resolution. So zoom level 14 will contain data at 1Kb resolution, zoom level 13 will contain data at 2Kb resolution, zoom level 12 at 4Kb, etc. If we know the original resolution of our data, we can calculate the number of zoom levels required to end up with one tile at the lowest resolution (thanks to @nv1ctus for the snippet below):

bins_per_tile = 256 	# the default, but can be set to anything
base_resolution = 1000  # 1Kb data coming in

tilesize = bins_per_tile * base_resolution
n_tiles = math.ceil(datasize / tilesize)

max_zoom = int(np.ceil(np.log2(n_tiles)))


So if our dataset has 3 billion rows and columns, then max_zoom will be 14.

Slicing data from the data matrix requires determining which rows and columns should be included in the tile.

tile_width = 2 ** (max_zoom - z) * bins_per_dimension

x_start = tile_x * tile_width
y_start = tile_y * tile_width

x_end = min(matrix.shape[0], x_start + tile_width)
y_end = min(matrix.shape[1], y_start + tile_width)

raw_tile = matrix[x_start:x_end,y_start:y_end]


And because this function is operating on the original, unaggregated, data and tile_width could be large we need to apply our downsampling aggregation function:

num_to_sum = 2 ** (max_zoom - z)
downsampled_tile = (np.nansum(
raw_tile.T.reshape(raw_tile.shape[1],-1,num_to_sum),
axis=2).T)


Note that for larger datasets, such as our Hi-C matrices, we pre-downsample the data for each zoom level so when a request hits the server, we can just quickly look up and retrieve the data for that zoom level.

## HiGlass

Over the past two and a half years we created HiGlass, a multiscale viewer for any type of large data. The interaction is the same as in online maps. You can pan and zoom and we only request resolution- and location- relevant data from the server. No matter how much data there is, the browser is never overloaded and interaction remains smooth and responsive. For proof, here is a 3 million by 3 million matrix displayed in a web browser.

Using a maps-like, tile based rendering, we can interactively navigate massive 3 million x 3 million matrices. On the left is just matrix and on the right is the matrix with an overlay showing the locations of the individual tiles. Because we are rendering directly on the client, we can adjust the color scale without having to re-retrieve data from the server.

This data spans over 3 billion base pairs. At the highest resolution, each pixel represents the number of contacts between two 1 kilo-base regions of the genome. The data is is pre-aggregated at 14 levels of resolution and stored on disk as HDF5 matrices according to the schema defined by the cooler format. The server, running on an AWS EC2 instance, fulfills each client tile request by slicing out the relevant region and returning it as a JSON object containing a base64 formatted string. Combining tile extraction with a caching server leads to 99% of responses being generated in less than 100ms. With a good internet connection, this makes for a fast user experience when browsing the data.

## Tiling other types of data

The example set by online maps can be adopted by nearly any other spatial-like data. As long as we can downsample our data and partition it into tiles, we can create a server component to power HiGlass. The previous example showed how matrices can be downsampled and decomposed into tiles. In this section we will demonstrate how we can use a generic function to generate tiles for HiGlass.

The Mandelbrot set can be rendered as a multiscale dataset. Zooming, limited to 25 levels to avoid hitting floating point precision artifacts. [fullscreen]

According to Wikipedia, “The Mandelbrot set is the set of complex numbers $c$ for which the function $f_{c}(z)=z^{2}+c$ does not diverge when iterated from $z=0$, i.e., for which the sequence $f_{c}(0)$, $f_{c}(f_{c}(0))$, etc., remains bounded in absolute value.” The essence of this definition is that for any complex number, $c$, we can calculate whether it is part of the Mandelbrot set by iteratively applying $f_{c}$. Furthermore, for any complex number $c$, we can calculate how many times (i.e. iterations) we need to apply $f_{c}$ before the absolute value of $c$ exceeds a certain threshold (e.g. 2). Because a complex number can be represented by two components, the real and the imaginary, any pixel with a $x$ and the $y$ value can be used to represent a complex number. By counting the number of iterations it takes to exceed the threshold we can calculate a color for each pixel and render the traditional Mandelbrot set (Figure 3).

So what about zooming? If we assign scales to the x- and y- axes of a figure and modify them as the user zooms in and out, then we can partition the figure into a grid of (x,y) pairs and iteratively calculate $f_{c}$ on the coordinates of each cell in the grid. As we zoom in, the granularity of the grid increases, the distance between cells shrinks and we have to recalculate the $f_{c}$ on the new grid. Using the tile-based approach described above, we can divide our grid into 256x256 tiles and offload the calculations to the server (AWS Lambda code available as a gist here). With a server-side tile API, we can use the standard HiGlass heatmap track to view the Mandelbrot set at multiple levels of resolution without having to pre-calculate anything or do heavy processing on the client. Interestingly, in this case, while we are taking slices of a window, we don’t have the highest resolution data. So instead of downsampling, we rely on a form of upsampling to calculate a higher resolution rendering of a smaller region.

## Summary

The three examples presented: online maps, large matrices, and the Mandelbrot set demonstrate three separate use cases where classical z, x, y indexed tiling can be used to display datasets far too large to display at once. By down/up-sampling and slicing, we can provide the client with only the data that it needs to display at the current zoom level and location. By using a generic front end renderer and tile fetcher like HiGlass, we can use different server implementation to provision it with manageable chunks of data to view.