The Rosmap gene expression profile data file was not uploaded due to its size, you can find it here: https://www.synapse.org/#!Synapse:syn2580853/wiki/409853

The gene cluster origin file is available in "csv/" folder, it is extracted and and transformed from BioGRID data available at: https://thebiogrid.org/download.php

The detailed report is in doc/report.pdf

For diagnosing patients with or without Alzheimer's Disease, given their gene expression profile, using gradient boosted trees and top-k clusters of Entrez IDs selected by t-test scores between samples of patients diagnosed with Alzheimer's Disease versus those who are not.

This section explains how to run the top_k.py module to calculate top-k t-test scores between clusters of Entrez IDs that produce the largest t-test score magnitudes between two means of patients labeled with Alzheimer's Disease (AD) and those with no cognitive impairment (NCI).

The calculations for student t-test use population standard deviation. Project report is doc/report.pdf.

1. Create an Amazon Web Service (AWS) account:

http://docs.aws.amazon.com/AmazonSimpleDB/latest/DeveloperGuide/AboutAWSAccounts.html

2. Create EC2 key-pair:

http://docs.aws.amazon.com/AWSEC2/latest/UserGuide/ec2-key-pairs.html#having-ec2-create-your-key-pair

3. Install AWS command line interface (CLI):

http://docs.aws.amazon.com/cli/latest/userguide/awscli-install-linux.html

Make sure to choose your OS from the left navigator.

4. Configure your AWS CLI:

http://docs.aws.amazon.com/cli/latest/userguide/cli-chap-getting-started.html

5. Create IAM group:

http://docs.aws.amazon.com/IAM/latest/UserGuide/id_groups_create.html

6. Attach group policy:

http://docs.aws.amazon.com/IAM/latest/UserGuide/id_groups_manage_attach-policy.html

Policies required:

AmazonEC2FullAccess
AmazonElasticMapReduceFullAccess

7. Create IAM user and add that user to group created in step 5:

http://docs.aws.amazon.com/IAM/latest/UserGuide/id_users_create.html

8. Create cluster:

aws emr create-cluster \
--name <1> \
--release-label emr-5.5.0 \
--applications Name=Spark Name=Hadoop \
--ec2-attributes KeyName=<2> \
--instance-type m3.xlarge \
--instance-count <3> \
--configurations <4> \
--use-default-roles

<1>: the name of your cluster.
<2>: the Ec2 key-pair created in step 2.
<3>: number of machines or instances to set up.
<4>: configuration of Spark variables, you can use the one provided in
"aws/config.json", which has Spark's dynamic allocation turned off and has
PySpark use Python3.

The above command outputs JSON format of your cluster ID, which is used for different things related to your AWS EMR cluster, such as:

• Describing cluster details:

aws emr describe-cluster --cluster-id j-35C7A973OSSRQ

• Adding more machines to your cluster.

aws emr add-instance-groups --cluster-id j-35C7A973OSSRQ --instance-groups InstanceCount=1,InstanceGroupType=core,InstanceType=m3.xlarge

http://docs.aws.amazon.com/emr/latest/ReleaseGuide/emr-spark-launch.html

Example:

aws emr create-cluster \
--name "Alzheimer-gene-distributed-computing" \
--release-label emr-5.5.0 \
--applications Name=Spark Name=Hadoop \
--ec2-attributes KeyName=pandora-id_rsa \
--instance-type m3.xlarge \
--instance-count 3 \
--configurations file:///home/hduser/Documents/spark/aws/config.json \
--use-default-roles

The command above creates a cluster named "Alzheimer-gene-distributed-computing" with 3 instances, 1 master instance and 2 core instances of type m3.xlarge, using key called "pandora-id_rsa", which is the key name I set up on AWS. The configuration file is given in local file path:

file:///home/hduser/Documents/spark/aws/config.json

9. Copy Rosmap and gene cluster files to master node.

• If your files are in Amazon S3. SSH into AWS EMR master node and do:

  aws s3 cp <bucket URL> <master node local URL>
  

  <bucket URL>: the s3://... URL to your data file.
  <local URL>: the HDFS path to save your data (HDFS host header not required).
  

• If your files are in your local machine, do:

  scp -i <keypair> <local file> hadoop@<master node address>:~/<file to paste>
  

  The -i flag is not required if you if you're using ssh-agent with your public keys set:

  scp <local file> hadoop@<master node address>:~/<file to paste>
  

10. SSH into master node and run spark-submit.

spark-submit --deploy-mode cluster <1> <2> <3> <4> <5>

IMPORTANT: all files must be on the master node (see step 6).

<1>: the spark application.
<2>: input Rosmap file path.
<3>: input gene cluster file path.
<4>: input top-k t-score value of each cluster to select.
<5>: the output file. The first line is time elapsed to calculate top-k
t-scores, and the rest have the schema:
(clusterID, t-score, ad mean, nci mean, ad pop. std., nci pop. std.)

11. Add spark step (OPTIONAL):

aws emr add-steps \
--cluster-id j-<1> \
--steps Type=spark,Name=MyApp,Args=[--deploy-mode,cluster,--conf,spark.yarn.submit.waitAppCompletion=false,s3://<2>/<3>,s3://<2>/<4>,s3://<2>/<5>,<6>,s3://<2>/<7>/], \
ActionOnFailure=CONTINUE

<1>: id of your cluster received from step 3.
<2>: your Amazon s3 bucket.
<3>: the spark application file name in your Amazon S3 bucket.
<4>: the rosmap patient gene expression file.
<5>: the gene cluster file.
<6>: top-k clusters of gene values with largest t-test scores.
<7>: output folder of resulting computations.

http://docs.aws.amazon.com/emr/latest/ReleaseGuide/emr-spark-submit-step.html

12. Terminate the cluster (OPTIONAL):

aws emr terminate-clusters --cluster-ids j-XXXXXXXXXXXX

http://docs.aws.amazon.com/emr/latest/ManagementGuide/UsingEMR_TerminateJobFlow.html

13. Access YARN web GUI through FoxyProxy (OPTIONAL):

• Download FoxyProxy add-on for your web browser. You may have to search for it in your browser's add-on website.

• Follow the instructions below to configure the FoxyProxy add-on:

  http://docs.aws.amazon.com/emr/latest/ManagementGuide/emr-connect-master-node-proxy.html

  A copy of FoxyProxy configuration file is in "aws/foxyproxy-settings.xml" for your convenience.

• SSH from the terminal, e.g.:

  ssh -ND 8157 [email protected]

• Enter the address into your browser with the FoxyProxy add-on, e.g.:

  http://ec2-34-224-26-209.compute-1.amazonaws.com:8088/cluster

This part of the application diagnoses patients using top-k t-test score gene clusters from the top-k cluster part of this project as features using Gradient Boosted Trees (GBT). The workflow is:

• Get libSVM file from Rosmap file (labeled_to_libSVM.py).
• Train the model on the libSVM file from step 1 (train_model.py).
• Use GBT from step 2 to diagnose a patient CSV file (diagnose.py).
• (OPTIONAL) calculate GBT k-fold cross validation (gbt_cross_validate.py).

1. If you don't have a libSVM file of the AD and NCI patients, run labeled_to_libSVM.py on the Rosmap file. This will automatically extra AD and NCI patients and convert the output to libSVM format.

Usage: labeled_to_libSVM.py <1> <2> <3> <4>

<1>: input Rosmap patient gene expression file.
<2>: input gene cluster file.
<3>: input top-k cluster feature file.
<4>: output libSVM file.

2. To train a model:

Usage: train_model.py <1> <2> <3>

<1>: input labeled libSVM file.
<2>: input number of tree iterations.
<3>: output of model.

3. To diagnose a patient, run diagnose.py:

Usage: diagnose.py <1> <2> <3> <4> <5>

<1>: input gradient boosted tree model.
<2>: input patient gene expression file (like Rosmap but without diagnosis)
<3>: input gene cluster file.
<4>: input top-k cluster features file.
<5>: output patient diagnosis file with schema (patient ID, 0.0 or 1.0), where
  0.0 means a prediction of no cognitive disease and 1.0 means the patient has
  been predicted to have Alzheimer's Disease.

IMPORTANT: schema of input file of patients gene expression profiles to diagnose: (patient ID, g1, g2, g3, ...), where g1, g2, g3, ... are gene expression values for the corresponding Entrez ID column.

4. To do k-fold cross validation:

Usage: gbt_cross_validate.py <1> <2> <3>

<1>: input labeled libSVM file.
<2>: input integer k folds.
<3>: input integer number of tree iterations.

5. Extract AD and NCI patients from Rosmap file for testing (OPTIONAL):

Usage: ad_nci_processor.py <1> <2> <3>

<1>: input Rosmap file.
<2>: output AD patients file (without diagnosis).
<3>: output NCI patients file (without diagnosis).