Reconstitution of the ERG Gene Expression Network Reveals New Biomarkers and Therapeutic Targets in ERG Positive Prostate Tumors.

Background: Despite a growing number of studies evaluating cancer of prostate (CaP) specific gene alterations, oncogenic activation of the ETS Related Gene (ERG) by gene fusions remains the most validated cancer gene alteration in CaP. Prevalent gene fusions have been described between the ERG gene and promoter upstream sequences of androgen-inducible genes, predominantly TMPRSS2 (transmembrane protease serine 2). Despite the extensive evaluations of ERG genomic rearrangements, fusion transcripts and the ERG oncoprotein, the prognostic value of ERG remains to be better understood.

MetaMiner (CF): a disease-oriented bioinformatics analysis environment.

MetaMiner (CF) is a data analysis platform for a broad range of CF researchers including wet lab biologists, bioinformaticians, clinicians, and chemists. To understand disease mechanisms and gain insight into complex biological actions, analysis of even simple gene interactions often requires integration of a variety of separate data resources such as literature, 3D molecular models, metabolic pathways, ontologies, small molecules, and drugs. Large-scale data sets from high-throughput screening assays, microarrays, and other data intensive procedures present an even greater challenge in data handling and analysis which now requires interdisciplinary teams of scientists with strikingly diverse backgrounds including computer scientists, statisticians, biologists, and clinicians.

Manual annotation of protein interactions.

Protein interactions are the basic building blocks for assembly of pathways and networks. Almost any biologically meaningful functionality (for instance, linear signaling pathways, chains of metabolic reactions, transcription factor dimmers, protein complexes of transcriptosome, gene-disease associations) can be represented as a combination of binary relationships between "network objects" (genes, proteins, RNA species, bioactive compounds). Naturally, the assembled pathways and networks are only as good as their "weakest" link (i.

Network analysis of human glaucomatous optic nerve head astrocytes.

Background: Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive.

Methods: To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs).

Results: Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors.

Genome-wide functional synergy between amplified and mutated genes in human breast cancer.

A single cancer cell contains large numbers of genetic alterations that in combination create the malignant phenotype. However, whether amplified and mutated genes form functional and physical interaction networks that could explain the selection for cells with combined alterations is unknown. To investigate this issue, we characterized copy number alterations in 191 breast tumors using dense single nucleotide polymorphism arrays and identified 1,747 genes with copy number gain organized into 30 amplicons.

Molecular definition of breast tumor heterogeneity.

Cells with distinct phenotypes including stem-cell-like properties have been proposed to exist in normal human mammary epithelium and breast carcinomas, but their detailed molecular characteristics and clinical significance are unclear. We determined gene expression and genetic profiles of cells purified from cancerous and normal breast tissue using markers previously associated with stem-cell-like properties. CD24+ and CD44+ cells from individual tumors were clonally related but not always identical.