Incorporating genomic, transcriptomic and clinical data: a prognostic and stem cell-like MYC and PRC imbalance in high-risk neuroblastoma.

Background: Previous studies suggested that cancer cells possess traits reminiscent of the biological mechanisms ascribed to normal embryonic stem cells (ESCs) regulated by MYC and Polycomb repressive complex 2 (PRC2). Several poorly differentiated adult tumors showed preferentially high expression levels in targets of MYC, coincident with low expression levels in targets of PRC2. This paper will reveal this ESC-like cancer signature in high-risk neuroblastoma (HR-NB), the most common extracranial solid tumor in children.

A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature).

c-Myc dysregulation is hypothesized to account for the 'stemness' - self-renewal and pluripotency - shared between embryonic stem cells (ESCs) and adult aggressive tumours. High-risk neuroblastoma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood. Using HR-NB as a platform, we performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures.

Correction: Foxf Genes Integrate Tbx5 and Hedgehog Pathways in the Second Heart Field for Cardiac Septation.

[This corrects the article DOI: 10.1371/journal.pgen.

The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation.

Human mutations in the cardiac transcription factor gene TBX5 cause congenital heart disease (CHD), although the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the nucleosome remodeling and deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart.

Identification of epigenetic modifications that contribute to pathogenesis in therapy-related AML: Effective integration of genome-wide histone modification with transcriptional profiles.

Background: Therapy-related, secondary acute myeloid leukemia (t-AML) is an increasingly frequent complication of intensive chemotherapy. This malignancy is often characterized by abnormalities of chromosome 7, including large deletions or chromosomal loss. A variety of studies suggest that decreased expression of the EZH2 gene located at 7q36.

Seq2pathway: an R/Bioconductor package for pathway analysis of next-generation sequencing data.

Unlabelled: Seq2pathway is an R/Python wrapper for pathway (or functional gene-set) analysis of genomic loci, adapted for advances in genome research. Seq2pathway associates the biological significance of genomic loci with their target transcripts and then summarizes the quantified values on the gene-level into pathway scores. It is designed to isolate systematic disturbances and common biological underpinnings from next-generation sequencing (NGS) data.

Systematic computation with functional gene-sets among leukemic and hematopoietic stem cells reveals a favorable prognostic signature for acute myeloid leukemia.

Background: Genes that regulate stem cell function are suspected to exert adverse effects on prognosis in malignancy. However, diverse cancer stem cell signatures are difficult for physicians to interpret and apply clinically. To connect the transcriptome and stem cell biology, with potential clinical applications, we propose a novel computational "gene-to-function, snapshot-to-dynamics, and biology-to-clinic" framework to uncover core functional gene-sets signatures.

Network models of genome-wide association studies uncover the topological centrality of protein interactions in complex diseases.

Background: While genome-wide association studies (GWAS) of complex traits have revealed thousands of reproducible genetic associations to date, these loci collectively confer very little of the heritability of their respective diseases and, in general, have contributed little to our understanding the underlying disease biology. Physical protein interactions have been utilized to increase our understanding of human Mendelian disease loci but have yet to be fully exploited for complex traits.

Methods: We hypothesized that protein interaction modeling of GWAS findings could highlight important disease-associated loci and unveil the role of their network topology in the genetic architecture of diseases with complex inheritance.