Winter 2021 newsletter now available | Winter 2021


HuGeAMP platform now powers multiple portals, with more underway

Over the past months we’ve been working on a complete overhaul of the Knowledge Portals (KPs), from the back end to the front pages. Almost all of the KPs now run on the Human Genetics Amplifier (HuGeAMP) platform, which offers faster data retrieval, integrated analysis methods, and a more intuitive and responsive web interface. The Common Metabolic Diseases Knowledge Portal (CMDKP), with its component disease-specific portals for cardiovascular and cerebrovascular disease, sleep disorders, and types 1 and 2 diabetes, is now fully launched. We have also moved the Musculoskeletal Knowledge Portal (MSK-KP) into the new framework, and the ALS Knowledge Portal will soon be installed in the HuGeAMP platform. The next portal to be released will be the new Lung Disease Knowledge Portal (LDKP), featuring results relevant to several lung diseases including COVID-19. The LDKP has been developed in collaboration with Drs. Michael Cho and Benjamin Raby, both of Brigham and Women's Hospital.

What’s different about the HuGeAMP framework?

A major difference in the new portals is that they display "bottom-line" meta-analyzed genetic associations, taking advantage of the multiple datasets in the resource (and accounting for sample overlap) to present consensus associations based on all currently available data. Associations from individual datasets are also still accessible, for researchers who would like to replicate their results using a specific study. Another major difference is that, thanks to closer collaboration with the Diabetes Epigenome Atlas, the new portals incorporate and display much more genomic data. Computational methods for analyzing genetic and genomic data are integrated into the framework, so that they can easily be re-run with each new data upload. And, in contrast to the sometimes sluggish performance of the old portals, the re-worked back end makes the new portals much more responsive.

New tools in the new portals

One impetus for the portal redesign, and a major focus of future development, is to facilitate the translation of genetic and genomic data into predictions that help researchers identify effector genes for diseases and traits. Most of the new tools reflect this focus, particularly the Predicted Effector Genes page, the Genomic Region Miner (GEM) on Region pages, and the Gene Finder tool. Find details on these and other new tools in our recent blog post. In general, all new tools and features are made available in the CMDKP; its component portals, and the independent portals such as the MSK-KP, will include only those tools that query data relevant to the portal’s area of focus.

New genetic association datasets

Our latest production release on January 29, 2021 brings the CMDKP to a total of 286 genetic association datasets and 346 traits, available for browsing and filtering on the CMDKP Genetic association datasets page. One of the highlights of this release is that the CMDKP now includes pre-publication results from TOPMed whole-genome sequencing for T2D, fasting glucose, and fasting insulin, from TOPMed investigators Jerome Rotter, Stephen Rich, Alisa Manning, Josée Dupuis, and James Meigs. Two other notable new datasets are the AMP T2D-GENES quantitative trait exome sequence analysis, including associations for 24 quantitative traits, and UCSD T1D GWAS meta-analysis, the largest-to-date T1D GWAS with nearly 500,000 subjects (Chiou et al. 2021, submitted).

We have re-worked the Genetic Association Interactive Tool (GAIT) in the new portal framework. GAIT now offers the ability to run custom aggregation tests using results from both the TOPMed whole genome sequencing and the AMP T2D-GENES quantitative trait exome sequence analysis, selecting custom variant filters and 4 different test methods for genes of interest.

Do you still use the old portals?

We are preparing to retire the old portals for T2D, cardiovascular and cerebrovascular disease, and sleep disorders. Each is accessible via a link on the home page of the new portal. The data in the old portals was last updated in summer 2020, and is completely represented in the new portals; however, not all of the features of the old portals are replicated in the new portals. If there are features of the old portals that you find valuable but are not available in the new framework, please let us know as soon as possible so that we can replicate and improve them. Thanks to those of you who have already offered suggestions!


Diabetes Epigenome Atlas (DGA) isn't just for diabetes anymore

In collaboration with DGA, we are developing a pipeline for for adding new functional genomic data to the CMDKP and its component portals. The pipeline includes: identifying new datasets of interest to all of the CMDKP disease areas; jointly prioritizing those datasets; loading them into DGA for processing and generation of genomic annotations; transfer of the annotations to the Data Coordinating Center at the Broad Institute; further analysis of the annotations using several computational methods; and representation of the analysis results on the Knowledge Portals. We are also working on better ways to categorize datasets in order to make it easier to view specific data types and tissue-specific results in the Portal visualizations: for example, transcription factor binding ChIP-seq results will now be grouped together, in contrast to viewing multiple tracks for individual TFs.

AMP-CMD Consortium launched

The Accelerating Medicines Partnership in Common Metabolic Diseases (AMP-CMD) Consortium was recently inaugurated, as the next iteration of the AMP-T2D collaboration. The goal of AMP-CMD is to generate data and develop tools and methods that will inform the identification of effector genes for type 2 diabetes and related traits, and to make these results broadly accessible in the CMDKP.

New informational resources

We have several new videos to keep you up to date on various aspects of the CMDKP and HuGeAMP projects:

Upcoming webinars and conferences

Webinars (all at noon, US Eastern time; connection info will be on our home page):

  • March 11: The HuGe Calculator tool from Knowledge Portal Labs (Peter Dornbos)
  • May 13
  • July 15

Upcoming conference presentations :

  • ENDO 2021 (March 20-23): invited talk and poster
  • American Diabetes Association Scientific Sessions (June 25-29): invited talk

Stay in touch!

Contact us with questions or suggestions; follow us on Twitter; join our LinkedIn group; or watch our videos on the Broad Institute YouTube channel.

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