STORM + InterMine: A partnership in the fight against cancer

In July 2018 Innovate UK awarded InterMine at the University of Cambridge and STORM Therapeutics a Knowledge Transfer Partnership (KTP). A KTP is a government program that helps businesses in the UK by linking them with an academic organisation — enabling them to bring in new skills and the latest academic thinking to deliver a specific, strategic innovation project.

The key objective of this particular project is to develop an analysis platform using the data warehouse InterMine to help STORM advance their cancer research.

Here we talk with Hendrik Weisser, Senior Bioinformatician at STORM, about this collaboration.

Can you tell me about this project?

Sure, my company (STORM) is partnering with InterMine in this project. We are going to develop a computational knowledge base for cancer drug discovery and RNA epigenetics, based on InterMine’s HumanMine database. We will extend InterMine by adding analysis tools, more biomedical data etc. to make it a bespoke platform to help us identify and validate drug targets.

Can you tell me more about STORM?

STORM Therapeutics is a drug discovery company focused on RNA epigenetics, developing small-molecule inhibitors of RNA-modifying enzymes for the treatment of cancer. We are a spin-out of Cambridge University, founded in 2015 by professors Eric Miska and Tony Kouzarides from the Gurdon Institute. You can find more information – and a cool animated video about RNA epigenetics – on our website, www.stormtherapeutics.com.

What do you hope to achieve?

For STORM, convenient access to available data on RNA-modifying enzymes, their roles in RNA epigenetics, and their associations to different cancers – both direct and via interaction partners – is vital for our efforts in target validation, indication prioritisation and patient stratification. A large amount of relevant data is publicly available but is scattered over many sources and not integrated, thus difficult and time-consuming to fully utilise. STORM’s vision is to develop an integrated database of relevant human biomedical data, that should enable our scientists to quickly view and interrogate the most pertinent data on target genes/proteins, but also allow us to easily perform bioinformatic analyses on these data.

What attracted you to InterMine? What makes InterMine a useful tool for drug discovery?

I found out about InterMine’s existence by chance and then quickly signed up to an InterMine training course at Cambridge University to learn more. I was impressed by the wealth of functionality offered by InterMine and by its sophisticated architecture that enables huge flexibility in dealing with different kinds of biological data. InterMine really represents the state of the art in terms of large-scale complex biomedical data integration. By focusing on extensibility and customisation and on enabling local installations, InterMine is able to serve a variety of research communities. These capabilities also make it an ideal fit for STORM’s requirements for an internal data management system that integrates diverse public data. The fact that InterMine is open-source, i.e. the code is and will stay available, is also important for us because it helps to ensure long-term maintainability.

—-

For more information see STORM’s website.

 

 

InterMine 2.1.0 release

We pushed out a few bug fixes and improvements:

  • FIX – “Update publications” data source failed when too many PubMed IDs were sent to the Entrez web service (Thank you to Norbert Auer!)
  • FIX – small bug for generating Python code
  • FIX – FASTA query web service times out when extensions are used (Thanks to Joel Richardson!)
  • FIX – Discontiguous CDS sequences and lengths not set properly
  • FIX – Some SO terms were not updated in 2.0 release
  • FIX – Region search: trying to leave “extended region” field blank results in error

See GitHub for details:

https://github.com/intermine/intermine/releases

How to Upgrade

Throughout the InterMine code, the InterMine version number is set via a global variable. Here’s an example:

# Maven will download the bio-core JAR with the correct version
compile group: 'org.intermine', name: 'bio-core', version: System.getProperty("bioVersion")

To change which InterMine version you are using , you will want to increment the value of the system property “imVersion” and “bioVersion“. These are located in  the “gradle.properties” file for your mine:

# gradle.properties in your mine
systemProp.imVersion=2.1.+
systemProp.bioVersion=2.1.+

Maven will now download, for example, the bio-core JAR of the latest version, e.g. “bio-core-2.1.0.jar”.

If you set the property to “2.1.+” you will get any small point releases that are published in the future. You can set the property to be 2.1.0 if you ONLY want to use version “2.1.0” and do not want to receive updates:

# gradle.properties to only get specific version
systemProp.imVersion=2.1.0
systemProp.bioVersion=2.1.0

Here is an example:

HumanMine upgrade to use the latest version.

InterMine 3.0 – SOLR

The next InterMine release will be InterMine 3.0 which will include SOLR. See our SOLR blog post for details.

We are currently testing SOLR with InterMine and should have a version ready for public beta testing early next month.

 

InterMine 2.0

We are excited to announce the official release of InterMine 2.0!

InterMine 2.0 includes some model updates, a big change in how InterMine itself is built, lots of new features, like a new UI, and a long list bug fixes. See the full list of updates here.

This release represents a large milestone for the InterMine team! Not only because we made big fundamental changes to the core InterMine data model and build system, but also because this release represents a major shift in philosophy for us. Previously InterMine was a big, monolithic, single piece of software. You downloaded the whole InterMine, you compiled the whole InterMine, you got the whole of InterMine. Instead, we are moving towards this idea of modularity and responsiveness. Smaller, independent libraries that are interconnected but can be used for tools and features separately or linked together.

Smaller decoupled InterMine packages will allow us to develop more features faster with less errors. InterMine maintainers might then have the flexibility to include (or not) the features in their mine, plug in their own tools, etc.

Version 2.0 represents a big step towards this goal!

A New Interface

A new feature in InterMine 2.0 is the ability to run our new UI, nicknamed “Blue Genes”. This app is in addition to the current webapp and offers a new and responsive search environment for your InterMine data.

Blue genes is a modern UI built in Clojure and provides a modern user experience.

  • Super fast response times
  • Interactive list upload
  • Redesigned “My account” section
  • Search autocomplete
  • Template and query builder result previews
  • .. lots more!

Once you have your InterMine updated to InterMine 2.0, there is a single command that will launch Blue Genes for your mine.

We are actively seeking feedback on Blue Genes, it’s still very much in the beta phase still, so please get in touch once you have some opinions!

Special Thanks

Thanks to everyone who helped test this release! Thanks Howie Motenko at MGI for your alpha testing and model insights. And a BIG thank you goes to Sam Hokin from the NCGR who spent a lot of time and effort helping improve InterMine! Thanks Sam and Howie! You are much appreciated.

Helpful Links

What exactly we changed (blog post)

Full list of GitHub tickets included this release

Docs on how to upgrade to 2.0

 

As always, please contact us if you have any questions or comments! We have an active twitter account, a discord server at chat.intermine.org, and a low traffic mailing list.

FlyMine 46.0 Released!

FlyMine has been updated to the latest version of FlyBase. All other data sets have also been updated to the newest versions and we have fixed a few bugs. See the data sources page for a full list of data and their versions. All data can be accessed through our comprehensive library of template searches or by building your own queries using the query builder.

 

Data model changes!

Our data model has changed slightly to make querying easier between mines.

  • Protein molecular weight is a float instead of an integer
  • We’ve added URLs for GO term evidence codes
  • Sequence Ontology (the basis for the InterMine data model) is updated, so lots of new data types added.

See our previous blog post for complete details of updates.

No more Anopheles

After listening to community feedback, we have decided to stop loading Anopheles data into FlyMine. However, as always, if there is a specific data set you are interested in, please contact us!

 

We have docs and videos, and for a full list of data sources available in FlyMine see the data sources list.

However, please do not hesitate to contact us should you require any further assistance. For all types of help and feedback email info@intermine.org.

HumanMine 5.0 released!

HumanMine has been updated to the latest version of NCBI Entrez Gene. All other data sets have also been updated to the newest versions and we have fixed a few bugs. See the data sources page for a full list of data and their versions. All data can be accessed through our comprehensive library of template searches or by building your own queries using the query builder.

 

New Data Source: GTEx

We added a new expression data set, GTEx. Here’s an example search:

Gene –> Tissue Expression

Tissue –> Gene expression

Data model changes!

Our data model has changed slightly to make querying easier between mines.

  • Protein molecular weight is a float instead of an integer
  • We’ve added URLs for GO term evidence codes
  • Sequence Ontology (the basis for the InterMine data model) is updated, so lots of new data types added.

See our previous blog post for complete details of updates.

 

We have docs and videos, and for a full list of data sources available in HumanMine see the data sources list.

However, please do not hesitate to contact us should you require any further assistance. For all types of help and feedback email info@intermine.org.

InterMine 2017 Fall Workshop – Biological Data Analysis using InterMine

University of Cambridge is hosting an InterMine workshop 27 October 2017.

The course is aimed at bench biologists and bioinformaticians who need to analyse their own data against large biological datasets, or who need to search against several biological datasets to gain knowledge of a gene/gene set, biological process or function. The exercises will mainly use the fly, human and mouse databases, but the course is applicable to anyone working with data for which an InterMine database is available.

The workshop is composed of two parts:

Part 1 (2.5 – 3 hours) will introduce participants to all aspects of the user interface, starting with some simple exercises and building up to more complex analysis encompassing several analysis tools and comparative analysis across organisms. No previous experience is necessary for this part of the workshop.

The following features of the InterMine web interface will be covered:

  • Search interfaces and advanced query builder
  • Automated analysis of sets, e.g gene sets, including enrichment statistics
  • Analysis workflows
  • Tools for cross-organism analysis between InterMine databases.
  • Web services

Part 2 (1 hour) will focus on the InterMine API and introduce running InterMine searches through Python and Perl scripts. While complete beginners are welcome, some basic knowledge of Perl, and/or Python would be an advantage. The InterMineR package will also be introduced. Those not interested in this part of the workshop are welcome to leave or there will be a more advanced exercise using the web interface available as an alternative.

See here for details: https://www.gen.cam.ac.uk/events/intermine-training

 

 

InterMine 2.0

InterMine 2.0 is a large, disruptive release. There are lots of exciting features, but they will require InterMine maintainers to update their mines. Usually devs are able to update their mines with a simple git pull request. In this case, they’ll have to take specific actions to make sure their software is up to date.

Model changes

Several changes and additions to the core InterMine data model were discussed and approved by the community. See here for specific details on the new core data model.

This means that it’s likely that an InterMine 2.0 webapp will require a database built by InterMine 2.0 code.

Blue Genes

InterMine 2.0 will come with detailed instructions on how to deploy the new InterMine user interface.

Come to the next InterMine community call to see a demo of the latest features!

Gradle

We’ve got a new software build system in the works. This will change the commands you use to build a data source and deploy your webapp. See a previous blog post for details.

Closer to the time, we’ll release detailed instructions on how to update your build system to work with the new tools. And as always the InterMine team will be on hand to answer any questions or issues on the community calls and the dev list and chat.

We hope to make the transition as easy as possible!

Software Dependencies

All software dependencies will need to be on the latest version.

  • Java 8
  • Tomcat 8.5.x
  • Postgres 9.4+

API Changes

We are making some non-backwards compatible changes to our API.

/user/queries will be moved to /queries

These three end points have a parameter called xml which holds the XML query. We are going to rename this parameter to be query (as we now accept JSON queries!) to match the syntax of all the other end points.

/query/upload
/template/upload
/user/queries (POST)

If this update is going to cause you any trouble at all, please let us know ASAP!

 

If you have any questions or concerns about any of these changes, please contact us or come along to the community calls.

 

 

 

Toxygates: exposing toxicogenomics datasets and linking with InterMine

This is a guest post from our colleague Johan Nyström-Persson, who works with ToxyGates and the NIBIOHN in Japan.

Toxygates (http://toxygates.nibiohn.go.jp) has been developed as a user-friendly toxicogenomics analysis platform at the Mizuguchi Lab, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) in Osaka since 2012. The first public release was in 2013. At this time, the main focus of Toxygates was exposing the Open TG-GATEs dataset, a large, systematically organised toxicogenomics dataset compiled during more than a decade by the Japanese Toxicogenomics Project (http://toxico.nibiohn.go.jp). This dataset consists of over 24,000 microarray samples. To make use of such a large dataset without time-consuming data manipulation and programming, it is necessary to have a rich user interface and access to many kinds of secondary data.

Toxygates allows anyone with a web browser to explore and analyse this data in context. Various kinds of filtering and statistical testing are available, allowing users to discover and refine gene sets of interest, with respect to particular compounds. For a reasonably sized data selection, hierarchical clustering and heat-maps can be displayed directly in the browser. Through TargetMine (http://targetmine.nibiohn.go.jp) integration (based on the InterMine framework), enrichment of various kinds is possible. Compounds can also be ranked according to how they influence genes of interest.

To support all of these functions, we came up with the concept of a “hybrid” data model which recognises that, while gene expression values by themselves may be viewed as a large matrix with a flat structure, secondary annotations of genes and samples, such as
proteins, pathways, GO terms or pathological findings, have an open-ended structure. Thus, we combine an efficient key-value store (for gene expressions) with RDF and linked data (for gene and sample annotations) to allow for both high performance and a flexible data structure.

Today, the project continues to evolve in new directions as a general transcriptomics data analysis platform. We have integrated Toxygates not only with TargetMine, but also with HumanMine, RatMine and MouseMine. Recently, users can also upload their own transcriptomics data and analyse it in context alongside Open TG-GATEs data. We may
also add more datasets in the future.

P1000874The current project members are Kenji Mizuguchi (project leader) and Chen Yi-An (NIBIOHN), Johan Nyström-Persson and Yuji Kosugi (Level Five), and Yayoi Natsume-Kitatani and Yoshinobu Igarashi (NIBIOHN).

InterMine 2.0 – Gradle

NB: To upgrade to InterMine 2.0 you must not have custom code in the core InterMine repository.

We have been planning out the tasks for future InterMine, and there is a lot of exciting projects on the horizon. We’re making InterMine more FAIR, putting InterMine in Docker and the cloud, our beautiful new user interface, Semantic Web and so on.

However a prerequisite for these exciting features is to update our build system. We are still using ant and it’s grown, let’s say, “organically” over the years — making updates and maintenance expensive and tedious.

After careful consideration and looking very seriously at other build and dependency management systems we’ve decided on Gradle. Gradle is hugely popular with a great community, and it’s used by such projects as Android, Spring and Hibernate. We were really impressed with Gradle’s power and flexibility, being able to run scripts in Gradle will give us the power we need to accomplish all our lofty goals.

Our goals for moving to Gradle

Managed dependencies

Our dependencies currently are manually managed — meaning if we need a third party library, we copy the JAR manually into our /lib directory. This is unsupportable for modern software and has resulted in lots of duplication and general heartache. With Gradle we can instead fetch dependencies automatically from online repositories.

A smaller repository

Implementing Gradle will allow us to replace many of our custom Ant-based facilities with Gradle infrastructure and widely-supported plugins. Our codebase will become smaller and more maintainable as a result.

A faster build

Currently, due to the way that InterMine implemented a custom project dependency system in Ant,  every InterMine JAR is compiled on every build and every time a webapp is deployed. This is unnecessary and wastes developer time. We will use Gradle’s sophisticated dependency management system to make the InterMine build more robust and efficient.

Maintainable, extensible, documented

The current Ant-based InterMine build system has been extended over the years as needed in an ad-hoc manner, and unfortunately no documentation exists. Adding a new ant task is a challenge, and debugging the current build process is time consuming and difficult. Moving to Gradle will base InterMine on a well maintained, extensible, documented and widely-used build system.

Simpler to run test suite

Currently, developers have to create property files and databases to run the full system tests, steps that are not straightforward to perform or execute. With Gradle’s help we hope to make this much easier, so that the wider InterMine community can benefit from running the InterMine test suite on their installations and code patches.

Simplicity

Finally, Gradle’s tests are in the same project as the main directory, thus cutting the number of separate projects will be cut in half. In addition, when building, the tests will be run automatically.

As an example, here is a new standard Gradle directory layout:

src/main/java
src/main/resources
src/test/java
src/test/resources

Currently our main and test projects are in different packages but in InterMine 2.0 these will be unified under single projects, as per standard practice.

What does this mean for you and your InterMine?

If you are currently maintaining an InterMine, moving to InterMine 2.0 is going to require a bit of effort on your part.

Operationally, commands such as database building and web application publishing are very likely to use Gradle commands rather than Ant targets or custom scripts. Users who have scripts to manage InterMine installations will need to adjust them appropriately. This shouldn’t require too much work.

InterMine users who have custom projects in the bio/sources directory to load data sources will need to make more adjustments. Project structures in InterMine 2.0 will not be the same as in earlier versions, since they will follow Gradle conventions rather than custom InterMine ones. However, the changes will not be major and we will provide a script to do as much automatic updating of custom sources as possible.

The greatest migration work will come for the most sophisticated operators who have directly patched core InterMine code. In this case, there are two options. Firstly, they can continue to patch and build core InterMine JARs themselves, though they will need to make adjustments for the Gradle build process. Secondly, we can work with them to add new configuration parameters to core InterMine to make such patching unnecessary, wherever possible. In both cases work will be required but the effort should not be large, since it is largely the structure of code that is changing rather than core logic or functionality.

 

This is a significant transition but one that should put InterMine on a solid base that lowers long-term maintenance costs and makes lots of exciting stuff possible in the future. As ever, please contact us if you have any concerns and we look forward to discussing this and any other subjects on community calls, blog comments, in our Discord chat and on the mailing list!

InterMine 2.0: Proposed Model Changes (III)

We have several new additions and changes to the InterMine core data model coming in InterMine 2.0 (due early 2018).

We had a great discussion on Thursday about the proposed changes. Below are the decisions we made.

Multiple Genome Versions, Varieties / Subspecies / Strains

 

We were not able to come to an agreement, but everyone still felt there might be a core data model that can allow for single and multiple genomes that will be useful for all InterMines.

The fundamental question is do we want organism to be per genome version, or allow organism to have several genome versions. In the latter case, we’d also need a helper class, e.g. “Strain”, that would contain information about the genome.

This topic is sufficiently complex that we’ve agreed to try a more formal process here, listing our different options, their potential impact etc. More information on this process soon!

Syntenic Regions

Proposed addition to the InterMine core data model

<class name="SyntenicRegion" extends="SequenceFeature" is-interface="true">
    <reference name="syntenyBlock" referenced-type="SyntenyBlock" reverse-reference="syntenicRegions"/>
  </class>
  
  <class name="SyntenyBlock" is-interface="true">    
   <collection name="syntenicRegions" referenced-type="SyntenicRegion" reverse-reference="syntenyBlock" />
   <collection name="dataSets" referenced-type="DataSet" />
   <collection name="publications" referenced-type="Publication" />
  </class>
  • We decided against making a SyntenyBlock a bio-entity, even though it would benefit from inheriting some references.
  • We also decided against the SyntenicRegion1 / SyntenicRegion1 format and instead they will be in a collection of regions.

GO Evidence Codes

Currently the GO evidence codes are only a controlled vocabulary and are limited to the code abreviation, e.g IEA. However UniProt and other data sources have started to use ECO ontology terms to represent the GO evidence codes instead.

We decided against changing the GO Evidence Code to be an ECO ontology term.

  • The ECO ontology is not comprehensive
  • Some mines have a specific data model for evidence terms

Instead we are going to add attributes to the GO Evidence Code:

  • Add a link to more information on the GO evidence codes
  • Add the full name of the evidence code.
  • Change GOEvidenceCode to be OntologyAnnotationEvidenceCode

We decided against loading a full description of the evidence code. The description on the GO site is a full page. We tried shortening but then it didn’t really add much information. Also there is no text file with the description available.

We are also going to move evidence to Ontology Annotation.

GOEvidenceCode will be renamed OntologyAnnotationEvidenceCode:

<class name="OntologyAnnotationEvidenceCode" is-interface="true">
 <attribute name="code" type="java.lang.String" />
 <attribute name="name" type="java.lang.String" />
 <attribute name="URL" type="java.lang.String" />
</class>

GOEvidence will be renamed OntologyEvidence:

<class name="OntologyEvidence" is-interface="true">
 <reference name="code" referenced-type="OntologyAnnotationEvidenceCode"/>
 <collection name="publications" referenced-type="Publication"/>
</class>

Evidence will move to OntologyAnnotation from GOAnnotation:

<class name="OntologyAnnotation" is-interface="true">
 <collection name="evidence" referenced-type="OntologyEvidence"/>
</class>

 

Ontology Annotations – Subject

Currently you can only reference BioEntities, e.g. Proteins and Genes, in an annotation. This is unsuitable as any object in InterMine can be annotated, e.g. Protein Domains. To solve this problem, we will add a new data type, Annotatable.

<class name="Annotatable" is-interface="true"> <attribute name="primaryIdentifier" type="java.lang.String"/> <collection name="ontologyAnnotations" referenced-type="OntologyAnnotation" reverse-reference="subject"/> <collection name="publications" referenced-type="Publication" reverse-reference="bioEntities"/> </class> <class name="OntologyAnnotation" is-interface="true"> <reference name="subject" referenced-type="Annotatable" reverse-reference="ontologyAnnotations"/> </class> <class name="BioEntity" is-interface="true" extends="Annotatable"/>

This will add complexity to the data model but this would be hidden from casual users with templates.

Also publications will be moved from BioEntity to Annotatable. This change will allow us to have both publication and annotations on things that are not BioEntities. primaryIdentifier will also be moved from BioEntity to `​Annotatable`.

Protein molecular weight

Protein.molecularWeight is going to be changed from an integer to a float.

Organism taxon ID

Organism.taxonId is going to be changed from an integer to a string.

Sequence Ontology update

The sequence ontology underpins the core InterMine data model. We will update to the latest version available.


If you would like to be involved in these discussions, please do join our community calls or add your comments to the GitHub tickets. We want to hear from you!