Extending lifespan with Hadoop and R

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Many experts believe that ageing can be delayed, this is one of the main goals of the the Institute of Healthy Ageing at University College London. I will present the results of my lifespan-extension …

Many experts believe that ageing can be delayed, this is one of the main goals of the the Institute of Healthy Ageing at University College London. I will present the results of my lifespan-extension research where we integrated publicly available genes databases in order to identify ageing related genes. I will show what challenges we met and what we have learned about the process of ageing.

Ageing is one of the fundamental mysteries in biology and many scientists are starting to study this fascinating process. I am part of the research group led by Dr Eugene Schuster at UCL Institute of Healthy Ageing. We experiment with Drosophila and Caenorhabditis elegans by modifying their genes in order to create long-lived mutants. The results of our experiments are quantified using high-throughput microarray analysis. Finally we apply information technology in order to understand how the ageing process works. I will show how we mine microarrays data in order to find the connections between thousands of genes and how we identify candidates for ageing genes.

We are interested in building a better understanding of genes functions by harnessing the large quantity of experimental microarray data in the public databases. Our hope is that after understanding the ageing process in simpler organisms we will be able to apply this knowledge in humans.

Cross-referencing expressions levels in thousands of genes and hundreds of experiments turned out to be a computationally challenging problem but Hadoop and Amazon cloud came to our rescue. In this talk I will present a case study based on our use of R with Amazon Elastic MapReduce and will give background on our bioinformatics challenges.

These slides were presented at ApacheCon Europe 2012:
http://www.apachecon.eu/schedule/presentation/3/

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  • 1. Extending lifespanwith R and Hadoop Radek Maciaszek Founder of DataMine Lab, CTO Ad4Game, studying towards PhD in Bioinformatics at UCL
  • 2. Agenda● Project background● Parallel computing in R● Hadoop + R● Future work (Storm)● Results and summary 2
  • 3. Project background● Lifespan extension - project at UCL during MSc in Bioinformatics● Bioinformatics – computer science in biology (DNA, Proteins, Drug discovery, etc.)● Institute of Healthy Ageing at UCL – lifespan is a king. Dozens of scientists, dedicated journals.● Ageing is a complex process or is it? C. Elegans (2x by a single gene DAF-2, 10x).● Goal of the project: find genes responsible for ageing 3 Caenorhabditis Elegans
  • 4. Primer in Bioinformatics● Central dogma of molecular biology● Cell (OS+3D), Gene (Program), TF (head on HDD)● How to find ageing genes (such as DAF-2)? 4 Images: Wikipedia
  • 5. RNA microarray DAF-2 pathway in C. elegans Source: Partridge & Gems, 2002 Source: Staal et al, 2003 5
  • 6. Goal: raw data → network Genes Network ● Pairwise comparisons of 10k x 10k genes + clustering 100 x 100 x 50 x 10 (~10k genes) 6
  • 7. Why R?● Incredibly powerful for data science with big data● Functional, scripting programming language with many packages.● Popular in mathematics, bioinformatics, finance, social science and more.● TechCrunch lists R as trendy technology for BigData.● Designed by statisticians for statisticians 7
  • 8. R exampleK-Means clusteringrequire(graphics)x <- rbind(matrix(rnorm(100, sd = 0.3), ncol = 2), matrix(rnorm(100, mean = 1, sd = 0.3), ncol = 2))colnames(x) <- c("x", "y")(cl <- kmeans(x, 2))plot(x, col = cl$cluster)points(cl$centers, col = 1:2, pch = 8, cex=2) 8
  • 9. R limitations & Hadoop● 10k x 10k (100MM) Fisher exact correlations is slow● Memory allocation is a common problem● Single-threaded● Hadoop integration: – Hadoop Streaming – Rhipe: http://ml.stat.purdue.edu/rhipe/ – Segue: http://code.google.com/p/segue/ 9
  • 10. Scaling R● Explicit – snow, parallel, foreach● Implicit – multicore (2.14.0)● Hadoop – RHIPE, rmr, Segue, RHadoop● Storage – rhbase, rredis, Rcassandra, rhdfs 10
  • 11. R and Hadoop ● Streaming API (low level)mapper.R#!/usr/bin/env Rscriptin <- file(“stdin”, “r”)while (TRUE) { lineStr <- readLines(in, n=1) line <- unlist(strsplit(line, “,”)) ret = expensiveCalculations(line) cat(data, “n”, sep=””)}close(in)jar hadoop-streaming-*.jar –input data.csv –output data.out –mapper mapper.R 11
  • 12. RHIPE● Can use with your Hadoop cluster● Write mappers/reduces using R only map <- expression({ z <- f <- table(unlist(strsplit(unlist( rhmr(map=map,reduce=reduce, map.values)," "))) inout=c("text","sequence") n <- names(f) ,ifolder=filename p <- as.numeric(f) ,ofolder=sprintf("%s- sapply(seq_along(n),function(r) out",filename)) rhcollect(n[r],p[r])) }) job.result <- rhstatus(rhex(z,async=TRUE), reduce <- expression( mon.sec=2) pre={ total <- 0}, reduce = { total <- total+sum(unlist(reduce.values)) }, post = { rhcollect(reduce.key,total) } ) 12 Example from Rhipe Wiki
  • 13. Segue● Works with Amazon Elastic MapReduce.● Creates a cluster for you.● Designed for Big Computations (rather than Big Data)● Implements a cloud version of lapply()● Parallelization in 2 lines of code!● Allowed us to speed up calculations down to 2h with the use of 16 servers 13
  • 14. Segue workflow (emrlapply) 14
  • 15. lapply()m <- list(a = 1:10, b = exp(-3:3))lapply(m, mean)$a[1] 5.5$b[1] 4.535125lapply(X, FUN)returns a list of the same length as X, each element of which isthe result of applying FUN to the corresponding element of X. 15
  • 16. Segue in a cluster> AnalysePearsonCorelation <- function(probe) { A.vector <- experiments.matrix[probe,] p.values <- c() for(probe.name in rownames(experiments.matrix)) { B.vector <- experiments.matrix[probe.name,] p.values <- c(p.values, cor.test(A.vector, B.vector)$p.value) } return (p.values)}> # pearson.cor <- lapply(probes, AnalysePearsonCorelation)Moving to the cloud in 3 lines of code! 16
  • 17. Segue in a cluster> AnalysePearsonCorelation <- function(probe) { A.vector <- experiments.matrix[probe,] p.values <- c() for(probe.name in rownames(experiments.matrix)) { B.vector <- experiments.matrix[probe.name,] p.values <- c(p.values, cor.test(A.vector, B.vector)$p.value) } return (p.values)}> # pearson.cor <- lapply(probes, AnalysePearsonCorelation)> myCluster <- createCluster(numInstances=5, masterBidPrice="0.68”, slaveBidPrice="0.68”, masterInstanceType=”c1.xlarge”, slaveInstanceType=”c1.xlarge”, copy.image=TRUE)> pearson.cor <- emrlapply(myCluster, probes, AnalysePearsonCorelation)> stopCluster(myCluster) 17
  • 18. R + HBaselibrary(rhbase)hb.init(serialize="raw")#create new tablehb.new.table("mytable", "x","y","z",opts=list(y=list(compression=GZ)))#insert some values into the tablehb.insert("mytable",list( list(1,c("x","y","z"),list("apple","berry","cherry"))))rows<-hb.scan.ex("mytable",filterstring="ValueFilter(=,substring:ber)")rows$get() https://github.com/RevolutionAnalytics/RHadoop/wiki/rhbase 18
  • 19. Discovering genes Topomaps of clustered genes This work was based on:A Gene Expression Map for Caenorhabditis elegans, Stuart K. Kim, et al., Science 293, 2087 (2001) 19
  • 20. Genes clusters Clusters based on Fisher exactpairwise genes comparisons Green lines represent random probes Red lines represent up-regulated probes Blue lines are down-regulated probes (in daf-2 vs daf-2;daf-16 experiment) 20
  • 21. Genes networks Network created with Cytoscape, platform for complex network analysis: http://www.cytoscape.org/ 21
  • 22. Future work - real time R● Hadoop has high throughput but for small tasks is slow. It is not good for continuous calculations.● A possible solution is to use Storm● Storm multilang can be used with any language, including R 22
  • 23. Storm R Storm may be easily integrated with third party languages and databases: ● Java ● Python ● Ruby ● Redis ● Hbase ● Cassandra Image source: Storm github wiki 23
  • 24. Storm R source("storm.R") initialize <- function() { emitBolt(list("bolt initializing")) } process <- function(tup) { word <- tup$tuple rand <- runif(1) if (rand < 0.75) { emitBolt(list(word + "lalala")) } else { log(word + " randomly skipped!") } } boltRun(process, initialize) https://github.com/rathko/storm 24
  • 25. Summary● It’s easy to scale R using Hadoop.● R is not only great for statistics, it is a versatile programming language.● Is ageing a disease? Are we all going to live very long lives? 25
  • 26. Questions?● References: http://hadoop.apache.org/ http://hbase.apache.org/ http://code.google.com/p/segue/ http://www.datadr.org/ https://github.com/RevolutionAnalytics/ https://github.com/rathko/storm 26