The Evolution of Oncology Companion Diagnostics from Signal Transduction to Immuno-Oncology.

Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved.

Personal genotypes are teachable moments.

There is an urgent need for effective genomics education for healthcare professionals. Recent analysis of an experimental genomics curriculum showed that medical students' examinations of their own genotypes provide a valuable learning experience. Such experiential learning has a long tradition in medical education and its application to genomics is enabled by increasingly powerful and decreasingly costly genome science and technology.

A call to action: training pathology residents in genomics and personalized medicine.

Genomics and "medical sequencing" will revolutionize clinical laboratory diagnostics as the foundation for the new era of personalized medicine. However, the medical profession lags far behind the technology and business communities in recognizing and preparing for this change. Pathologists must take the lead in the application of genomics technologies, including whole-genome sequencing, to laboratory diagnostics and personalized medicine.

Customized care 2020: how medical sequencing and network biology will enable personalized medicine.

Applications of next-generation nucleic acid sequencing technologies will lead to the development of precision diagnostics that will, in turn, be a major technology enabler of precision medicine. Terabyte-scale, multidimensional data sets derived using these technologies will be used to reverse engineer the specific disease networks that underlie individual patients' conditions. Modeling and simulation of these networks in the presence of virtual drugs, and combinations of drugs, will identify the most efficacious therapy for precision medicine and customized care.

Sequence databases: integrated information retrieval and data submission.

This unit describes the NCBI's Entrez database browser. Entrez integrates DNA and protein sequence data, three dimensional structures, and taxonomic information with its associated abstracts and citations contained in PubMed (MEDLINE). It is possible to search the Entrez information space using conventional search queries (authors, gene names, map location) as well as by bibliographic associations (articles that are related to one another) and sequence homology.

Sequence databases: integrated information retrieval and data submission.

This unit provides an overview of biomedical information resources, focusing on sequence data, structure information, and the associated literature, and also discusses how nucleotide sequence data gets into the databases in the first place. Some specific databases covered here are MEDLINE, GenBank, and Entrez.

Genome-wide atlas of gene expression in the adult mouse brain.

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain.

Neurogenomics: at the intersection of neurobiology and genome sciences.

Neurogenomics is the study of how the genome as a whole contributes to the evolution, development, structure and function of the nervous system. It includes investigations of how genome products (transcriptomes and proteomes) vary in time and space. Neurogenomics differs markedly from the application of genome sciences to other systems, particularly in the spatial category, because anatomy and connectivity are paramount to our understanding of function in the nervous system.

Genome informatics: current status and future prospects.

This article reviews recent advances in genomics and informatics relevant to cardiovascular research. In particular, we review the status of (1) whole genome sequencing efforts in human, mouse, rat, zebrafish, and dog; (2) the development of data mining and analysis tools; (3) the launching of the National Heart, Lung, and Blood Institute Programs for Genomics Applications and Proteomics Initiative; (4) efforts to characterize the cardiac transcriptome and proteome; and (5) the current status of computational modeling of the cardiac myocyte. In each instance, we provide links to relevant sources of information on the World Wide Web and critical appraisals of the promises and the challenges of an expanding and diverse information landscape.

Biomedical informatics for proteomics.

Success in proteomics depends upon careful study design and high-quality biological samples. Advanced information technologies, and also an ability to use existing knowledge to the full, will be crucial in making sense of the data. Despite its genome-scale potential, proteome analysis is at a much earlier stage of development than genomics and gene expression (microarray) studies.

Molecular archeology of L1 insertions in the human genome.

Background: As the rough draft of the human genome sequence nears a finished product and other genome-sequencing projects accumulate sequence data exponentially, bioinformatics is emerging as an important tool for studies of transposon biology. In particular, L1 elements exhibit a variety of sequence structures after insertion into the human genome that are amenable to computational analysis. We carried out a detailed analysis of the anatomy and distribution of L1 elements in the human genome using a new computer program, TSDfinder, designed to identify transposon boundaries precisely.

The human pregnane X receptor: genomic structure and identification and functional characterization of natural allelic variants.

The pregnane X receptor (PXR)/steroid and xenobiotic receptor (SXR) transcriptionally activates cytochrome P4503A4 (CYP3A4) when ligand activated by endobiotics and xenobiotics. We cloned the human PXR gene and analysed the sequence in DNAs of individuals whose CYP3A phenotype was known. The PXR gene spans 35 kb, contains nine exons, and mapped to chromosome 13q11-13.

Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.

Variation in the CYP3A enzymes, which act in drug metabolism, influences circulating steroid levels and responses to half of all oxidatively metabolized drugs. CYP3A activity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically expressed at high levels in a minority of Americans of European descent and Europeans (hereafter collectively referred to as 'Caucasians'). Only people with at least one CYP3A5*1 allele express large amounts of CYP3A5.

Experimental annotation of the human genome using microarray technology.

The most important product of the sequencing of a genome is a complete, accurate catalogue of genes and their products, primarily messenger RNA transcripts and their cognate proteins. Such a catalogue cannot be constructed by computational annotation alone; it requires experimental validation on a genome scale. Using 'exon' and 'tiling' arrays fabricated by ink-jet oligonucleotide synthesis, we devised an experimental approach to validate and refine computational gene predictions and define full-length transcripts on the basis of co-regulated expression of their exons.

Genes, themes and microarrays: using information retrieval for large-scale gene analysis.

The immense volume of data resulting from DNA microarray experiments, accompanied by an increase in the number of publications discussing gene-related discoveries, presents a major data analysis challenge. Current methods for genome-wide analysis of expression data typically rely on cluster analysis of gene expression patterns. Clustering indeed reveals potentially meaningful relationships among genes, but can not explain the underlying biological mechanisms.

Classical oncogenes and tumor suppressor genes: a comparative genomics perspective.

We have curated a reference set of cancer- related genes and reanalyzed their sequences in the light of molecular information and resources that have become available since they were first cloned. Homology studies were carried out for human oncogenes and tumor suppressors, compared with the complete proteome of the nematode, Caenorhabditis elegans, and partial proteomes of mouse and rat and the fruit fly, Drosophila melanogaster. Our results demonstrate that simple, semi-automated bioinformatics approaches to identifying putative functionally equivalent gene products in different organisms may often be misleading.

Frequent human genomic DNA transduction driven by LINE-1 retrotransposition.

Human L1 retrotransposons can produce DNA transduction events in which unique DNA segments downstream of L1 elements are mobilized as part of aberrant retrotransposition events. That L1s are capable of carrying out such a reaction in tissue culture cells was elegantly demonstrated. Using bioinformatic approaches to analyze the structures of L1 element target site duplications and flanking sequence features, we provide evidence suggesting that approximately 15% of full-length L1 elements bear evidence of flanking DNA segment transduction.