Genetic program activity delineates risk, relapse, and therapy responsiveness in multiple myeloma.

Despite recent advancements in the treatment of multiple myeloma (MM), nearly all patients ultimately relapse and many become refractory to multiple lines of therapies. Therefore, we not only need the ability to predict which patients are at high risk for disease progression but also a means to understand the mechanisms underlying their risk. Here, we report a transcriptional regulatory network (TRN) for MM inferred from cross-sectional multi-omics data from 881 patients that predicts how 124 chromosomal abnormalities and somatic mutations causally perturb 392 transcription regulators of 8549 genes to manifest in distinct clinical phenotypes and outcomes.

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

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.

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen.

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments.

KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer.

mutation is a common canonical mutation in colorectal cancer, found at differing frequencies in all consensus molecular subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of mutation across the CMS spectrum.

Low HERV-K(C4) copy number is associated with type 1 diabetes.

Complement component C4 (C4) is a highly variable complement pathway gene situated ∼500 kb from DRB1 and DQB1, the genes most strongly associated with many autoimmune diseases. Variations in C4 copy number (CN), length, and isotype create a highly diverse gene cluster in which insertion of an endogenous retrovirus in the ninth intron of C4, termed HERV-K(C4), is a notable component. We investigated the relationship between C4 variation/CN and type 1 diabetes.

Identification of context-dependent motifs by contrasting ChIP binding data.

Motivation: DNA binding proteins play crucial roles in the regulation of gene expression. Transcription factors (TFs) activate or repress genes directly while other proteins influence chromatin structure for transcription. Binding sites of a TF exhibit a similar sequence pattern called a motif.

Derivation of burn scar depths and estimation of carbon emissions with LIDAR in Indonesian peatlands.

During the 1997/98 El Niño-induced drought peatland fires in Indonesia may have released 13-40% of the mean annual global carbon emissions from fossil fuels. One major unknown in current peatland emission estimations is how much peat is combusted by fire. Using a light detection and ranging data set acquired in Central Kalimantan, Borneo, in 2007, one year after the severe peatland fires of 2006, we determined an average burn scar depth of 0.

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells.

Background: Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes.

Chd1 regulates open chromatin and pluripotency of embryonic stem cells.

An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells.

Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.

Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression.

Role of the murine reprogramming factors in the induction of pluripotency.

Induced pluripotent stem (iPS) cells can be obtained from fibroblasts upon expression of Oct4, Sox2, Klf4, and c-Myc. To understand how these factors induce pluripotency, we carried out genome-wide analyses of their promoter binding and expression in iPS and partially reprogrammed cells. We find that target genes of the four factors strongly overlap in iPS and embryonic stem (ES) cells.