T.R.Golub, D.K.Slonim, P.Tamayo, C.Huard, M.Gaasenbeek, J.P.Mesirov, H.Coller, M.L.Loh, J.R.Dowing, M.A.Caligiuru, C.D.Bloomfield, E.S.Lander
Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring
SCIENCE Vol286 15 October 1999
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・DNAマイクロアレイを使った病気診断のはしり。
・データ:Our initial leukemia data set consisted of 38 bone marrow samples (27 ALL, 11 AML) obtained from acute leukemia patient at the time of diagnosis. Affymetrix製。ヒト遺伝子6817プローブ
・AML:acute myeloid leukemia、 ALL:acute lymphoblastic leukemia
・実験1:Class Discovery 38サンプルをSOMs(self-organizing maps)でクラス分け → 結果、4クラスに分離
・実験2:Class Prediction 38サンプルをALLかAMLのどちらかにクラス分け
Predictorとなる50遺伝子の抽出法→"neighborhood analysis"→各遺伝子ごとの発現量をベクトルと見なし、理想状態(理想ベクトル)との距離(Pearson correlation coefficient)で判定。
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The average prediction strength was lower for samples from one laboratory that used a very different protocol for sample preparation.」
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Expression levels for each gene are normalized across the samples such that the mean is 0 and the SD is 1.」
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Most importantly, the technique of class prediction can be applied to distinctions relating to future clinical outcome, such as drug response or survival.」