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Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease.


ABSTRACT: While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post-challenge analysis identified a novel expression-based risk marker, PHF19, which has recently been found to have an important biological role in multiple myeloma. Lastly, we show that a simple four feature predictor composed of age, ISS, and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.

SUBMITTER: Mason MJ 

PROVIDER: S-EPMC7326699 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease.

Mason Mike J MJ   Schinke Carolina C   Eng Christine L P CLP   Towfic Fadi F   Gruber Fred F   Dervan Andrew A   White Brian S BS   Pratapa Aditya A   Guan Yuanfang Y   Chen Hongjie H   Cui Yi Y   Li Bailiang B   Yu Thomas T   Chaibub Neto Elias E   Mavrommatis Konstantinos K   Ortiz Maria M   Lyzogubov Valeriy V   Bisht Kamlesh K   Dai Hongyue Y HY   Schmitz Frank F   Flynt Erin E   Dan Rozelle   Danziger Samuel A SA   Ratushny Alexander A   Dalton William S WS   Goldschmidt Hartmut H   Avet-Loiseau Herve H   Samur Mehmet M   Hayete Boris B   Sonneveld Pieter P   Shain Kenneth H KH   Munshi Nikhil N   Auclair Daniel D   Hose Dirk D   Morgan Gareth G   Trotter Matthew M   Bassett Douglas D   Goke Jonathan J   Walker Brian A BA   Thakurta Anjan A   Guinney Justin J  

Leukemia 20200214 7


While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in ne  ...[more]

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