Research

A comprehensive transcript index of the human genome generated using microarrays and computational approaches

Eric E Schadt^{* 1} , Stephen W Edwards^{* 1} , Debraj GuhaThakurta¹ , Dan Holder² , Lisa Ying² , Vladimir Svetnik² , Amy Leonardson¹ , Kyle W Hart³ , Archie Russell¹ , Guoya Li¹ , Guy Cavet¹ , John Castle¹ , Paul McDonagh⁴ , Zhengyan Kan¹ , Ronghua Chen¹ , Andrew Kasarskis¹ , Mihai Margarint¹ , Ramon M Caceres¹ , Jason M Johnson¹ , Christopher D Armour¹ , Philip W Garrett-Engele¹ , Nicholas F Tsinoremas⁵ and Daniel D Shoemaker¹

¹Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, WA 98034, USA

²Merck Research Laboratories, W42-213 Sumneytown Pike, POB 4, Westpoint, PA 19846, USA

³Rally Scientific, 41 Fayette Street, Suite 1, Watertown, MA 02472, USA

⁴Amgen Inc, 1201 Amgen Court W, Seattle, WA 98119, USA

⁵The Scripps Research Institute, Jupiter, FL 33458, USA

author email corresponding author email* Contributed equally

Genome Biology 2004, 5:R73doi:10.1186/gb-2004-5-10-r73

Published:	23 September 2004

Subject areas: Genome studies, Methods, Bioinformatics

Abstract

Background

Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22.

Results

The combination of microarray data with extensive genome annotations resulted in a set of 28,456 experimentally supported transcripts. This set of high-confidence transcripts represents the first experimentally driven annotation of the human genome. In addition, the results from genomic tiling suggest that a large amount of transcription exists outside of annotated regions of the genome and serves as an example of how this activity could be measured on a genome-wide scale.

Conclusions

These data represent one of the most comprehensive assessments of transcriptional activity in the human genome and provide an atlas of human gene expression over a unique set of gene predictions. Before the annotation of the human genome is considered complete, however, the previously unannotated transcriptional activity throughout the genome must be fully characterized.