Human Protein Atlas オンラインセミナー

A Human Protein Atlas

Mathias Uhlen, AlbaNOva University Center, Royal Institute of Technology, Stockholm, Sweden

The completion of the human genome sequence has opened up a possibility for global expression profiling of human tissues and cells, allowing for comparative studies between normal and disease tissues. A multi-disciplinary research was initiated in July 2003 to allow for systematic exploration of the human proteome using antibody-based tissue proteomics, combining high-throughput generation of mono-specific antibodies (affinity-purified) with protein profiling in human tissues and cells using tissue microarrays. Analysis of protein expression patterns was performed on tissue and cell microarrays containing >700 spots of normal and cancer tissues as well as in vitro cultured cells. The results are presented in a publicly available database containing images and data from protein profiling. Each image has been manually annotated and curated by a certified pathologist to provide a knowledge base for functional studies and to allow searches and queries about protein profiles in normal and disease tissue. Our results suggest that it should be possible to extend this analysis to a majority of all human proteins thus providing a valuable tool for medical and biological research. The data from the systematic exploration of the human proteome within the Human Protein Atlas (HPA) (www.proteinatlas.org) has provided new opportunities to identify various types of biomarkers with in silico based methods. A subset of the antibodies has been selected for an extended analysis in tumors from defined patient cohorts. Specially designed TMA:s, including clinical data associated with the corresponding patients, were created and immunostained with antibodies against selected targets. Each such TMA contains over 100 different tumors from patients with a defined tumor type. The extended analysis showed that for several potential biomarkers, protein expression levels correlated with various clinico-pathological parameters including overall survival of respective patients. Using this strategy several new markers of potential clinical importance can be discovered and validated.

（要約）
ヒトゲノム配列の組織・細胞への網羅的発現解析により、正常組織と疾患組織の比較が可能になりました。2003年7月より、ヒトプロテオームの系統的探索が開始され、抗体を利用した組織プロテオミクスと同時に、ハイスループットでモノクローナル抗体が作製されています。このモノクローナル抗体はアフィニティ精製され、ヒト組織・細胞におけるマイクロアレイによるタンパク質プロファイリングが行われています。700箇所以上の正常組織・細胞および癌組織・細胞に対するマイクロアレイによるタンパク質発現パターンを解析し、解析結果をデータベース化し、画像やタンパク質プロファイリングが利用できるように一般公開しています。　画像はすべて病理学者によってアノテートされ、正常・疾患組織におけるプロファイル・機能研究の情報となります。これをヒトタンパク質の大部分に拡大することは、医学・生化学研究に大いに役立つであろうと考えられます。

また、Human Protein Atlas (HPA) (www.proteinatlas.org) による、ヒトプロテオーム網羅的探索データを利用し、in silicoによるバイオマーカーの同定の可能性も開かれます。特定の患者コホートの腫瘍において、一解析ごとに異なる抗体を選択します。こうして選択した標的別の抗体を用いた免疫組織染色データから、組織マイクロアレイ(TMA)データを作成します。このTMAには、同じ腫瘍タイプでも異なる患者由来の100種類以上の腫瘍サンプルを用いています。このような拡張解析から、バイオマーカー候補のタンパク質発現レベルと全生存を含む臨床病理学的なパラメーターが相関していることが示されています。この手法で臨床的に重要な新規マーカーを発見・バリデートすることが可能です。

今すぐオンラインセミナーを視聴する

Mathias Uhlén, Ph.D.

Mathias Uhlén is Professor of Microbiology at the Royal Institute of Technology (KTH), Stockholm, Sweden. Dr Uhlén is member of the Royal Swedish Academy of Engineering Science (IVA), the Royal Swedish Academy of Science (KVA) and the European Molecular Biology Organization (EMBO). He is Vice-President of the European Proteomics Association (EuPA) and member of the Human Proteome Organization (HUPO) council. Dr Uhlén has more than 280 publications in bioscience with the focus on the development and use of affinity reagents in biotechnology and biomedicine.

Dr Uhlén is currently working on the Human Protein Atlas (HPA) program, with the aim to systematically map the human proteome. In October 2007, version 3.0 of the Protein Atlas was published (www.proteinatlas.org) with more than 2.8 million high-resolution images representing 2,621 human proteins.

Dr Uhlén has founded several companies, including Pyrosequencing AB (Biotage AB), Affibody AB, SweTreeGenomics AB, Magnetic Biosolutions AB, Creative Peptides AB and Atlas Antibodies AB. He has received numerous awards, including The Svedberg prize in 1992, the Göran Gustavsson prize in 1993, the gold medal of the Royal Swedish Academy of Engineering Sciences in 2004, the Most Noble Order of the Seraphim - the Order of His Majesty the King in 2004, the Jerker Porath award and the Akzo Nobel Award in 2005 and the HUPO Distinguished Achievement Award in 2006.

Dr Uhlén is member of the Board of Directors of Biotage AB (publ), Skanditek AB (publ), Nordiag ASA (publ), Novozymes A/S (publ), Affibody AB, Atlas Antibodies AB, KTH Holding AB and SweTree Genomics AB.

References

Berglund et al (2008) “The epitope space of the human proteome” Protein Science 17, 606-613.

Uhlen, M (2008) “Affinity as a tool on life science” Biotechniques, in press (April)

Mathivanan et al (2008) “Human Proteinpedia enables sharing of human protein data” Nature Biotechnol. 26(2):164-7.

Hober S and Uhlén M. (2008) “Human protein atlas and the use of microarray technologies” Curr Opin Biotechnol. 19(1):30-5.

Björling et al (2008) “A web-based tool for in silico biomarker discovery based on tissue-specific protein profiles in normal and cancer tissues” Mol Cell Proteomics, in press (April)

Barbe et al (2008) “Toward a confocal subcellular atlas of the human proteome” Mol Cell Proteomics. 7(3):499-508

Uhlen M. (2007) “Mapping the human proteome using antibodies” Mol Cell Proteomics 6(8):1455-6.