With Pith

Ethan Petuchowski

First Glance at Genomics With ADAM and Spark

At work, we have a Spark cluster. One of my first responsibilities was to make it more reliable and efficient. So I looked on Github to see how people actually use Spark, and what magic they use to get their clusters not to crash in the process. This is how I found ADAM, “a genomics analysis platform built using Avro, Spark, and Parquet”. Then I looked in the repo’s contributors list, and watched a few lectures by Frank Nothaft and Matt Massie, two of the project’s main contributors. What I heard there was pretty cool.

In short, they’re looking to build systems that will “one day” recommend more effective treatments for diseases including cancer and Alzheimer’s within an hour of receiving a patient’s DNA sample. They describe several components of what needs to be done to make [research toward] this possible.

ADAM according to YouTube

See the references at the bottom of this post.

They didn’t explain much of the actual genomics, though what they did explain of that, they did with laudable clarity. In essence, the first step is to assemble (“sequence”) a large number of small strips of DNA into a single massive (250 GB) chain (per sample per person), even in the presence of small errors in the small strips. Ok now the the second step is to take the data from multiple samples from multiple people, and find anomalies that correlate historically with the likelihood to end up being diagnosed with a particular disease. These anomalies may be on the scale of a few single-character changes scattered around the DNA, again in the presence of mistakes in the transcription of the DNA. So statistical techniques are used (from what I remember, Poisson random sampling methods and binomial Bayesian methods, and Chi-squared independence tests) to evaluate the confidence in the correlations.

According to the lecturers, currently, techniques for doing this sort of computation and analysis relies on code written by PhD students in genomics, who are not so interested in writing high quality code, as learning about genomics and finishing their dissertations. Therefore, there are many (compressed) file formats, and processing subsystems written in every programming language you can think of. These subsystems are assembled together by piping data through the filesystem between each compoenent. Many of these subsystems are inherent unscalable.

All these are issues the researchers at the Big Data Genomics project are trying to solve using ADAM. They reported in SIGMOD 2015 to have achieved a 28x speedup and 63% cost reduction over current genomics pipelines. The Big Data Genomics project is a collaboration between researchers at the AMPLab at UC Berkeley, and other genetics and cloud- computing research institutions and companies. They note that their ADAM pipeline infrustructure is able to accommodate analyses from other areas of scientific research as well, including astronomy and neuroscience.

Producing a high-quality human genome currently takes 120 hours using a “single, beefy node”. Their improvements involve using map-reduce (via Spark), and columnar storage (via Avro & Parquet) to distribute the workload across a scalable cluster, so their 28x speedup is probably something people are happy about.

A major issue faced by genomics researchers is the proprietary nature of the data. This means that researchers must collect and process their own data, which is heavily human and computer labor intensive. The humongous (I mean really…) nature of the datasets means that the only practical means of transferring them is by shipping boxes of hard drives. As data collection gets easier, and the amount of data available explodes, even shipping boxes will become impractical. So the vision is to keep the data in the Simple Storage Service (S3) hosted by Amazon Web Services (AWS) so that it can be operated on via Spark without being copied into an institution’s private data center. This is currently more dream than reality, but seems like the logical step because of how Big the Data is.

Another major issue faced by genomics researchers is the large number of (open and proprietary) genomics data formats, and the quirks/bugs in their implementations. The ADAM team’s solution to this is their large, fixed schema, created using Apache Avro. This schema is designed to be able to accommodate whatever genetics research you may want to do. To allow ADAM to ingest your format, you write a transformation from your format to their standard Avro schema. Then all the applications built-in to ADAM for analyzing the data are available to you.

ADAM, according to the paper

The software architecture is (explicitly) based to a large extent on the Internet’s OSI model. It also has 7 layers, starting with a few storage layers, going to a schema layer, going to compute and transform layers, then to an application layer. The point is, like the OSI model, to make it easier to implement on top of existing components, to make it portable in the important dimensions across scientific disciplines and execution environments; and also to allow the implementations of each layer to be swapped out over time as the hardware, compute software, and relevant scientific algorithm ecosystems evolve.

They proceed to discuss several pipelines (one genomics, the other astronomy) that they implemented (mainly) around the needs of Spark and their AWS (virtual) hardware. They note that their re-implementation provides several bug-fixes with respect to algorithm implementations in reference genetics software components. Plus, each of the reference components can only communicate through disk I/O, while the Spark data pipeline keeps data in memory until the end. This is reminiscent of the original insight of Spark: speedup over Hadoop MapReduce by keeping as much data in memory as possible throughout the job.

Datasets in genomics, astronomy, and many other scientific fields involve a coordinate system. In genomics, it is generally a 1-dimensional string of nucleotides (A, C, G, T), which serves as a convenient abstraction over what is really a collection of molecules, each containing a packaged collection of DNA polymers in a complex 3D shape, crammed into the nucleus of a cell (I think, pg. 8). There is an assumed independence of data between distant regions of the 1D string.

The Region Join Algorithm

To figure out which regions of the 1D space were acquired by this sample from this “non-reference” human being, it is matched up with a “reference” (a.k.a. “idealized”) human genome, generated by aggregating many people together. What they use Spark for is to figure out which regions of the reference genome were sequenced in this real DNA sample. They call it “convex hull” (see below for definition), because to generalize to multi-dimensional spaces that’s the right way to see it, but for 1-Dimension, you’re really just looking to line-up sub- lines along a big line, and that would have been a simpler way to explain it if I’m not mistaken.

This “region join” can be implemented by (a) shipping the reference genome to each node, and having them output which part was matched for each input data- strip, or (b) repartitioning and sorting the datasets in such a way that puts the joinable data from each dataset on the same machine in sorted order (which I believe is part of the Spark API), and then iterating through both, and “zipping” them together.

The output of that stage is a powerful primitive for higher-level algorithms that researchers will want to run.


Part of the Hadoop concept is that you get data locality because MapReduce (or Spark) schedules your computations on the HDFS nodes that already happen to be holding the relevant data. However, this conflicts with their goal of being able to store like 100s of petabytes of data. They can’t really maintain the cost of having enough (even virtual) machines up and storing their giant datasets. So they opted to store the data in Amazon S3 (distributed storage) “buckets”. This increases job start (and sometimes finish) duration, but lowers costs.

This reminds me of how the default method for using the “Databricks cloud platform” assumes that you are storing your dataset in S3 buckets, and the data will be loaded (remotely) into the relevant EMR (virtual machine) nodes when the user of an interactive Spark session (or scheduled script) asks for them.

They store the data as in Parquet files. They wrote their own Parquet “row chunk” index file, that Spark then uses to figure out how to intelligently paralellize file [system block] reads, and not read (too much) more of the files than is really necessary. This is done with the help of a query predicate pushdown mechanism. If I’m not mistaken, all this stuff is really cool, but now it’s built-in to Spark with the help of the Catalyst optimizer, which I think came out after this paper did.

Cost and Performance

In their experiments, ADAM is way faster and cheaper than existing implementations of each of its components in almost all genomic situations. Taking the whole pipeline as a single system, then it’s always way cheaper and faster. This is also true for the astronomy dataset and task. They achieve near linear performance scaling (i.e. when adding more machines to the cluster) in almost all components.

Diversion: Convex Hull

  • Convex set/shape — for any two points in the shape, the line connecting them is also part of the shape
  • Convex hull — the smallest convex set that contains a given subset of points in the space
  • Convex hull in 1-Dimension
    • given a set of lines, the smallest range of the line that contains the start and end of every given line (right?)
    • given a set of points, just find the line connecting the smallest and largest point (right?)