JP2010176661A - 薬物を選択する方法 - Google Patents
薬物を選択する方法 Download PDFInfo
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- JP2010176661A JP2010176661A JP2010004875A JP2010004875A JP2010176661A JP 2010176661 A JP2010176661 A JP 2010176661A JP 2010004875 A JP2010004875 A JP 2010004875A JP 2010004875 A JP2010004875 A JP 2010004875A JP 2010176661 A JP2010176661 A JP 2010176661A
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- 229940061414 trileptal Drugs 0.000 description 1
- 229940072651 tylenol Drugs 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 229940020965 zoloft Drugs 0.000 description 1
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Abstract
【解決手段】 患者に対する薬物を選択するのに使用されるデータベースを構築する方法であって、コンピュータシステムにおいて、1パネルの遺伝子に対する複数の遺伝子型を受け取るステップと、前記遺伝子型に基づいて指定される複数の薬物プロフィールを受け取るステップと、各薬物プロフィールが前記遺伝子型の1種類に関連するように前記複数の遺伝子型と前記薬物プロフィールを保存するステップとを含む方法。
【選択図】 なし
Description
本方法は、患者から生物学的サンプルを得るステップ、および1パネルの遺伝子について患者の遺伝子型を得るステップを含む。一般に、遺伝子型を決定する遺伝子のパネルは、少なくとも3種類のチトクロムP450遺伝子を含む。チトクロムP450遺伝子は、表1に記載するP450遺伝子から選択することができる。例えば、少なくとも3種類のチトクロムP450遺伝子は、CYP2D6、1A2および2C19をコードすることができる。抗うつ薬を選択する実施形態においては、4種類のチトクロムP450遺伝子(例えば、CYP2D6、2C19、3A4および1A2をコードする遺伝子)の遺伝子型を得ることができる。別の実施形態においては、少なくとも5種類のチトクロムP450遺伝子(例えば、CYP1A1、1A2、2D6、2C19および3A4をコードする遺伝子)の遺伝子型を得ることができる。さらに別の実施形態においては、少なくとも10種類のチトクロムP450遺伝子(例えば、CYP1A1、1A2、1B1、2A6、2B6、2C8、2C9、2C18、2C19、2D6、2E1、3A4および3A5をコードする遺伝子)の遺伝子型を得ることができる。これらのチトクロムP450遺伝子の各々に対する対立遺伝子を表1に示す。
ゲノムDNAは、一般に、遺伝子型を決定するために使用されるが、mRNAを使用することもできる。ゲノムDNAは、一般に、末梢血液サンプルなどの生物学的サンプルから抽出されるが、組織(例えば、口の内側の粘膜を削り取ったもの、あるいは腎臓または肝臓組織由来のもの)を含めた他の生物学的サンプルから抽出することができる。例えば、フェノール抽出を含めて、常法によって、血液または組織サンプルからゲノムDNAを抽出することができる。あるいは、QIAamp(登録商標)Tissue Kit(Qiagen、Chatsworth、CA)、Wizard(登録商標)Genomic DNA精製キット(Promega)、A.S.A.P.(商標)Genomic DNA単離キット(Boehringer Mannheim、Indianapolis、IN)などのキットを用いてゲノムDNAを抽出することができる。
パネル上の各遺伝子について遺伝子型を決定した後に薬物を選択することができる。一般に、選択は、チトクロムP450遺伝子の遺伝子型を、各チトクロムP450遺伝子によってコードされる各チトクロムP450酵素の薬物代謝能力と相関させるステップを含む。パネル上の別の標的遺伝子、例えば、セロトニントランスポーターおよび/またはドーパミントランスポーター遺伝子の遺伝子型を患者の薬物応答能力と相関させることができる。
本明細書に記載する技術は、コンピュータプログラム中の具体的な命令を実行するプロセッサを備えるコンピュータシステムにおいて実施することができる。このコンピュータシステムは、患者の遺伝子型を受け取るステップに基づいて薬物プロフィールを出力するようにすることができる。特に、コンピュータプログラムは、個々の患者に最も適切な薬物(例えば、向精神薬)をシステムに選択させる命令を含むことができる。
一実施形態においては、製品は、オリゴヌクレオチドプライマーを含む組成物である。一般に、このような組成物は、各10〜50ヌクレオチド長の第1のオリゴヌクレオチドプライマーおよび第2のオリゴヌクレオチドプライマーを含むだろう。これらは、哺乳動物由来のゲノムDNAと混合し、PCR条件に供して、標的遺伝子内の目的領域に対応する核酸生成物を産生することができる。組成物は、緩衝剤、およびPCRに必要な他の試薬(例えば、DNAポリメラーゼまたはヌクレオチド)を含むこともできる。また、組成物は、複数の核酸生成物を生成できるように1種類または複数の追加のオリゴヌクレオチドプライマー対(例えば、5、10、15または20個のプライマー対)を含むことができる。
患者のCYP450遺伝子型
この実験は、選択的セロトニン再取り込み阻害薬に対して非定型的な応答を示す若者の評価結果に光を当てたものである。欠損を生じる以下のCYP2D6対立遺伝子、すなわち、*2(1661G>Cおよび2850C>T)、*3(2549A>del)、*4(1661G>Cおよび1846G>A)、*10(100C>T、1661G>Cおよび1846G)、*17(1023C>Tおよび2850C>T)を検出した。CYP2D6(*5 del)の欠失は、PCR増幅後の電気泳動によって検出された。CYP2D6遺伝子の縦列重複は、重複に特異的な配列を増幅し、電気泳動後に検出することによって検出された。
増幅プライマー:
CYP2D6 Prenest B F 5'-CCA GAA GGC TTT GCA GGC TTC A-3' (塩基1281〜1302、配列番号1)
CYP2D6 Prenest B R 5'-ACT GAG CCC TGG GAG GTA GGT A-3' (塩基6357〜6378、配列番号2)
CYP2D6 (C100T)
増幅プライマー:
・CYP2D6 (100)B f 5'GGC CTA CCC TGG GTA AGG GCC TGG AGC AGG A -3' (塩基1579〜1594、配列番号3)
・CYP2D6 (100)B r 5'-/5Bio/ CCT GGT CGA AGC AGT AT-3' (塩基2394〜2411、配列番号4)
プローブおよび安定剤:
CYP2D6 C100T野生型 5'-/5Cy3/GCA CGC TAC C-3'(塩基1700〜1710、配列番号5)
CYP2D6 C100T多型 5'-/5Cy5/GCA CGC TAC T -3'(塩基1700〜1710、配列番号6)
CYP2D6 C100T安定剤 5'CAC CAG GCC CCC TGC CAC TG -3'(塩基1711〜1731、配列番号7)
増幅プライマー:
・CYP2D6 (1023)B f 5'-CCT GCT CAC TCC TGG TAG CC -3'(塩基2394〜2413、配列番号8)
・CYP2D6(1023)B r 5'-/5Bio/ CTG TTT CAT GTC CAC GAC C-3' (塩基2760〜2779、配列番号9)
プローブおよび安定剤:
CYP2D6(1023)野生型 5'-/5Cy3/TGC CCA TCA C-3' (塩基2632〜2642、配列番号10)
CYP2D6(1023)多型 5'-/5Cy3/TGC CCA TCA T -3' (塩基2632〜2642、配列番号11)
CYP2D6(1023)安定剤 5'CCA GAT CCT GGG TTT CGG GCC GCG -3' (塩基2643〜2667、配列番号12)
注: このアンプリコンには多型が2つある。
・CYP2D6(1661,1846)B f 5'- CAG AGG CGC TTC TCC G -3' (塩基3266〜3282、配列番号13)
・CYP2D6(1661,1846)B r 5'- /5Bio/CTC GGT CTC TCG CTC CGC AC -3' (塩基3630〜3650、配列番号14)
プローブおよび安定剤:
CYP2D6(1661)野生型 5'-/5Cy3/CTT CTC CGT G -3' (塩基3266〜3276、配列番号15)
CYP2D6(1661)多型 5'-/5Cy3/CTT CTC CGT C -3' (塩基3266〜3276、配列番号16)
CYP2D6(1661)安定剤 5'-TCC ACC TTG CGC AAC TTG GGC CTG GG -3' (塩基3277〜3303、配列番号17)
CYP2D6(1846)野生型 5'-/5Cy3/CCA CCC CCA G -3' (塩基3460〜3470、配列番号18)
CYP2D6(1846)多型 5'-/5Cy3/CCA CCC CCA A -3' (塩基3460〜3470、配列番号19)
CYP2D6(1846)安定剤 5'-GAC GCC CCT TTC GCC CCA ACG -3' (塩基3471〜3492、配列番号20)
増幅プライマー:
CYP2D6(A2549delおよびC2850T)B f 5'- TGA GAC TTG TCC AGG TGA AC -3' (塩基4001〜4022、配列番号21)
・CYP2D6(A2549delおよびC2850T)B r 5'-/5Bio/ CCC AGA TGG GCT CAC GCT GC-3' (塩基4558〜4578、配列番号22)
プローブおよび安定剤:
CYP2D6(2549)野生型 5'-/5Cy3/ACT GAG CAC A -3' (塩基4161〜4171、配列番号23)
CYP2D6(2549)多型 5'-/5Cy3/ ACT GAG CAC G-3' (塩基4161〜4171、配列番号24)
CYP2D6(2549)安定剤 5'-GGA TGA CCT GGG ACC CAG CCC AGC C3' (塩基4172〜4199、配列番号25)
CYP2D6(2850)野生型 5'-/5Cy3/GAG AAC CTG C -3' (塩基4462〜4472、配列番号26)
CYP2D6(2850)多型 5'-/5Cy3/ GAG AAC CTG T-3' (塩基4462〜4472、配列番号27)
CYP2D6(2850)安定剤 5'-GCA TAG TGG TGG CTG ACC TGT TCT CTG -3' (塩基4473〜4500、配列番号28)
A. PreNest(初期増幅):
CYP2D6 PreNest B CYP2D6(C1661G)、CYP2D6(G1846A)、CYP2D6(A2549Del)、CYP2D6(C100T)、CYP2D6(C2850T)およびCYP2D6(C1023T)多型の初期PreNest PCRを、1個のサンプル当たり以下の試薬、すなわち、0.6μL 25μM PreNest B F、0.6μL 25μM PreNestB R、2.5μL 10mM dNTP、39.55μL dH2O、5.0μL Expand Buffer 3(Roche)、0.75μL Expand Enzyme Mix (Roche)、および1.0μlゲノムDNAを用いて総容積50μLで実施した。PCRは、94℃2分間の保持、次いで、94℃30秒間の変性、67℃30秒間のアニーリングおよび68℃7分間の伸長を30サイクル、続いて、72℃10分間の最終伸長によって実施された。予想PCR産物は、約4.8〜5Kbであった。
(C100T)ネステッドPCR(nested PCR)は、初期PreNest Bアンプリコン1μlをテンプレートとして使用して実施された。このPCRの産物を使用してCYP2D6(C100T)突然変異を検出し、以下の試薬、すなわち、1.0μl 25μM CYP2D6(100)B f、1.0μl 25μM CYP2D6(100)B r、12.5μl Qiagen Hot Start Master Mix、および9.5μl dH2Oを用いる(25μL総容積)。PCRは、95℃15分間の保持、次いで、95℃30秒間の変性、57℃30秒間のアニーリングおよび72℃1分間の伸長を30サイクル、続いて、72℃7分間の最終伸長によって実施された。
(C1023T)ネステッドPCRは、PreNest B産物1μlをテンプレートとして使用して実施された。このPCRの産物を使用してCYP2D6(C1023T)突然変異を検出し、以下の試薬、すなわち、1.0μl 25μM CYP2D6(1023)B f、1.0μl 25μM CYP2D6(1023)B r、12.5μl Amplitaq Gold Master Mix、および9.5μl dH2Oを用いる(25μL総容積)。PCRは、95℃10分間の保持、次いで、95℃30秒間の変性、59℃30秒間のアニーリングおよび72℃1分間の伸長を30サイクル、続いて、72℃7分間の最終伸長によって実施された。
(C1661GおよびG1846A)ネステッドPCRは、PreNest B産物1μlをテンプレートとして用いて実施された。このPCRの産物を使用してCYP2D6(C1661G)およびCYP2D6(G1846A)突然変異を検出し、以下の試薬、すなわち、1.0μl 25μM CYP2D6(1661、1846)B f、1.0μl 25μM CYP2D6(1661、1846)B r、12.5μl 2X Amplitaq Gold Master Mix、および9.5μl dH2Oを用いる(25μL総容積)。PCRは、95℃10分間の保持、次いで、95℃30秒間の変性、63℃30秒間のアニーリングおよび72℃1分間の伸長を30サイクル、続いて、72℃7分間の最終伸長によって実施された。
(A2549DelおよびC2850T)ネステッドPCRは、PreNest B産物1μlをテンプレートとして使用して実施された。このPCRの産物を使用してCYP2D6(A2549Del)およびCYP2D6(C2850T)突然変異を検出し、以下の試薬、すなわち、1.0μl 25μM CYP2D6(2549、2850)B f、1.0μl 25μM CYP2D6(2549、2850)B r、12.5μl 2X Amplitaq Gold Master Mix、および9.5μl dH2Oを用いる(25μL総容積)。PCRは、95℃10分間の保持、次いで、95℃30秒間の変性、57℃30秒間のアニーリングおよび72℃1分間の伸長を30サイクル、続いて、72℃10分間の最終伸長によって実施された。
ドーパミントランスポーター、ドーパミン受容体、トリプトファンヒドロキシラーゼ、セロトニン受容体およびCOMT遺伝子の遺伝子型の決定
表7の以下のプローブおよびプライマーは、ドーパミントランスポーター(DAT1、SLC6A3)、ドーパミン受容体(DRD1、DRD2、DRD3、DRD4およびDRD5)、トリプトファンヒドロキシラーゼ(TPH)、セロトニントランスポーター(5-HTT)、セロトニン受容体(HTR1A、HTR1B、HTR1D、HTR2AおよびHTR2C)およびCOMT遺伝子の遺伝子型を検出するために作製することができる。
97人の患者において、CYP2D6、CYP2C19および5HTTR遺伝子の遺伝子型を上記方法によって決定した。実施例1に示したように、CYP2D6 *2、*3、*4、*10、*17および*5 del対立遺伝子、CYP2C19 *2(A,B)、*3、*4、*5(A,B)、*6、*7および*8対立遺伝子、ならびに短い/長い形態の5HTTR遺伝子を評価した。
10人の患者において、CYP2D6、CYP2C19、CYP3A4、CYP1A2およびHTR2A遺伝子の遺伝子型を上記方法によって決定した。5HTTR遺伝子の遺伝子型は、遺伝子の多型領域を、その領域に隣接するプライマーを用いて増幅することによって決定された。反応生成物は、電気泳動(Agilent Technologies)によってサイズ分けされた。CYP3A4 *1B、*2、*5、*6、*12、*13、*15A、*17および*18A対立遺伝子、CYP1A2 *1F対立遺伝子およびHTR2A 102多型が検出された。
本発明をその詳細な説明に関連して説明したが、上述の記述は、説明のためのものであって、添付した特許請求の範囲の範囲によって定義される本発明の範囲を限定するものではないことを理解されたい。他の態様、利点および改変も以下の特許請求の範囲の範囲内にある。
Claims (16)
- 患者に対する薬物を選択するのに使用されるデータベースを構築する方法であって、
(a) コンピュータシステムにおいて、1パネルの遺伝子に対する複数の遺伝子型を受け取るステップと、
(b) 前記遺伝子型に基づいて指定される複数の薬物プロフィールを受け取るステップと、
(c) 各薬物プロフィールが前記遺伝子型の1種類に関連するように、前記複数の遺伝子型と前記薬物プロフィールを保存するステップと、
を含む方法。 - 少なくとも1つの薬物プロフィールによって薬物が特定される、請求項1に記載の方法。
- 前記薬物が、前記薬物プロフィールに含まれる複数のカテゴリーの1つに入る、請求項2に記載の方法。
- 各カテゴリーが、安全に使用できる薬物、注意して使用すべき薬物、使用したときに厳重に監視すべき薬物、回避すべき薬物、およびそれらの組み合せからなる群から選択される、請求項3に記載の方法。
- 前記薬物プロフィールによって、前記患者の遺伝子型に対する薬物候補の範囲が特定される、請求項2に記載の方法。
- 実行されたときにプロセッサにオペレーションを実施させる実行可能命令を含むコンピュータプログラム製品であって、前記オペレーションが、
(a) 1パネルの遺伝子に対する複数の遺伝子型を受け取り、
(b) 前記遺伝子型に基づいて指定される複数の薬物プロフィールを受け取り、
(c) 各薬物プロフィールが、前記遺伝子型の1種類に関連するように前記遺伝子型と前記薬物プロフィールを保存する、
ことを含む、コンピュータプログラム製品。 - 患者に対する薬物を選択する方法であって、
(a) コンピュータシステムにおいて1パネルの遺伝子に対する患者の遺伝子型を受け取るステップと、
(b) 遺伝子型に関連する複数の薬物プロフィールを含むデータベースにおいて、前記患者の遺伝子型に関連する薬物プロフィールを特定するステップと、
(c) 前記患者の遺伝子型を受け取るステップに応答して、前記特定された薬物プロフィールを出力するステップと、
を含む方法。 - 使用者が、前記患者の遺伝子型を前記コンピュータシステムに入力する、請求項7に記載の方法。
- 前記患者の遺伝子型が、患者の遺伝子型を決定するのに使用される装置から直接受け取られる、請求項7に記載の方法。
- 前記特定された薬物プロフィールが、いくつかの薬物の順位を含む、請求項7に記載の方法。
- 前記順位が特異的コファクターに基づく、請求項10に記載の方法。
- 前記特定された薬物プロフィールを出力する前に、前記順位を調節するステップをさらに含む、請求項10に記載の方法。
- 前記順位が、前記患者が有する遺伝子型多型を受け取ることに基づいて調節される、請求項12に記載の方法。
- 前記順位が、前記患者に関係する臨床反応を受け取ることに基づいて調節される、請求項12に記載の方法。
- 前記臨床反応が患者の家族によるものである、請求項14に記載の方法。
- 実行されたときにプロセッサにオペレーションを実施させる実行可能命令を含むコンピュータプログラム製品であって、前記オペレーションが、
(a) 1パネルの遺伝子に対する患者の遺伝子型を受け取り、
(b) 遺伝子型に関連する複数の薬物プロフィールを含むデータベースにおいて、前記患者の遺伝子型に関連する薬物プロフィールを特定し、
(c) 前記患者の遺伝子型を受け取るステップに応答して、前記特定された薬物プロフィールを出力する、
ことを含む、コンピュータプログラム製品。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011154800A (ja) * | 2010-01-26 | 2011-08-11 | Sumitomo Chemical Co Ltd | 発光装置およびその製造方法 |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8688385B2 (en) * | 2003-02-20 | 2014-04-01 | Mayo Foundation For Medical Education And Research | Methods for selecting initial doses of psychotropic medications based on a CYP2D6 genotype |
EP2393028B1 (en) | 2003-02-20 | 2015-09-30 | Mayo Foundation For Medical Education And Research | Methods for selecting antidepressant medications |
ES2825949T3 (es) * | 2004-09-30 | 2021-05-17 | Vanda Pharmaceuticals Inc | Métodos para administrar iloperidona |
AU2006320633A1 (en) * | 2005-11-29 | 2007-06-07 | Children's Hospital Medical Center | Optimization and individualization of medication selection and dosing |
US20100273147A1 (en) * | 2006-01-19 | 2010-10-28 | Valenti Samuel R | Medical diagnostic system and methods |
US8380539B2 (en) * | 2006-05-09 | 2013-02-19 | University Of Louisville Research Foundation, Inc. | Personalized medicine management software |
WO2008052167A2 (en) * | 2006-10-27 | 2008-05-02 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Methods to identify patients at risk of developing adverse events during treatment with antidepressant medication |
WO2008076434A2 (en) * | 2006-12-18 | 2008-06-26 | Theragenetics | Predicting a response to risperidone |
US8099298B2 (en) | 2007-02-14 | 2012-01-17 | Genelex, Inc | Genetic data analysis and database tools |
US7795033B2 (en) * | 2007-03-19 | 2010-09-14 | The United States Of America As Represented By The Department Of Health And Human Services | Methods to predict the outcome of treatment with antidepressant medication |
AU2008310577A1 (en) * | 2007-10-12 | 2009-04-16 | Patientslikeme, Inc. | Self-improving method of using online communities to predict health-related outcomes |
WO2010048020A1 (en) * | 2008-10-20 | 2010-04-29 | Epitome Pharmaceuticals Limited | Methods and systems for improved pharmaceutical intervention in coagulation control |
US8315815B2 (en) | 2008-12-30 | 2012-11-20 | The Invention Science Fund I, Llc | Computational methods and systems for suggesting modulators of CYP450 as treatment options |
US8321151B2 (en) | 2008-12-30 | 2012-11-27 | The Invention Science Fund I, Llc | Computational methods and systems for treatment in relation to modulation of CYP450 enzyme activity |
US8073632B2 (en) * | 2008-12-30 | 2011-12-06 | The Invention Science Fund I, Llc | Computational methods and systems for treatment in relation to modulation of CYP450 enzyme activity |
WO2010126577A1 (en) | 2009-04-30 | 2010-11-04 | Patientslikeme, Inc. | Systems and methods for encouragement of data submission in online communities |
US9558320B2 (en) * | 2009-10-26 | 2017-01-31 | Genomas, Inc. | Physiogenomic method for predicting drug metabolism reserve for antidepressants and stimulants |
WO2012054681A2 (en) * | 2010-10-21 | 2012-04-26 | Mayo Foundation For Medical Education And Research | Methods for selecting medications for treating patients having attention-deficit hyperactivity disorder |
CN105956398A (zh) * | 2010-11-01 | 2016-09-21 | 皇家飞利浦电子股份有限公司 | 包括专有测试的特许使用费的自动化代理的体外诊断测试 |
US20120209081A1 (en) * | 2011-02-11 | 2012-08-16 | Abbas Sadeghian | Method of preventing patient injury |
US9779214B2 (en) | 2012-01-06 | 2017-10-03 | Molecular Health Gmbh | Systems and methods for personalized de-risking based on patient genome data |
WO2014055398A1 (en) * | 2012-10-05 | 2014-04-10 | Siemens Healthcare Diagnostics Inc. | Method for detecting an increased risk or incidence of colorectal cancer |
US10210312B2 (en) | 2013-02-03 | 2019-02-19 | Youscript Inc. | Systems and methods for quantification and presentation of medical risk arising from unknown factors |
US20140243211A1 (en) | 2013-02-28 | 2014-08-28 | Indiana University Research & Technology Corporation | Blood biomarkers for suicidality |
US20140274764A1 (en) * | 2013-03-15 | 2014-09-18 | Pathway Genomics Corporation | Method and system to predict response to treatments for mental disorders |
US20170253928A1 (en) * | 2013-03-15 | 2017-09-07 | Pathway Genomics Corporation | Method and system to predict response to treatments for mental disorders |
US20190055603A1 (en) * | 2015-04-28 | 2019-02-21 | Proove Biosciences, Inc. | System and method for processing genotype information relating to drug metabolism |
WO2016176482A1 (en) * | 2015-04-28 | 2016-11-03 | Proove Biosciences, Inc. | System and method for processing genotype information relating to non-opioid response |
US10395759B2 (en) | 2015-05-18 | 2019-08-27 | Regeneron Pharmaceuticals, Inc. | Methods and systems for copy number variant detection |
KR20180018706A (ko) | 2015-06-12 | 2018-02-21 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 조합된 게놈 및 임상 위험 평가를 이용한 자살경향의 예측 |
CA3105451A1 (en) | 2017-05-12 | 2018-11-15 | Indiana University Research And Technology Corporation | Precision medicine for treating and preventing suicidality |
CN111742370A (zh) | 2017-05-12 | 2020-10-02 | 密歇根大学董事会 | 个体和队列药理学表型预测平台 |
JP7320345B2 (ja) * | 2017-10-27 | 2023-08-03 | シスメックス株式会社 | 遺伝子解析方法、遺伝子解析装置、遺伝子解析システム、プログラム、および記録媒体 |
WO2019083024A1 (ja) * | 2017-10-27 | 2019-05-02 | シスメックス株式会社 | 遺伝子解析方法、遺伝子解析装置、管理サーバ、遺伝子解析システム、プログラム、および記録媒体 |
US10950354B1 (en) * | 2018-03-02 | 2021-03-16 | Allscripts Software, Llc | Computing system for pharmacogenomics |
US11894139B1 (en) | 2018-12-03 | 2024-02-06 | Patientslikeme Llc | Disease spectrum classification |
CN110643689A (zh) * | 2019-10-29 | 2020-01-03 | 陕西佰美基因股份有限公司 | 一种检测HTR2A基因rs6313位点的TaqMan探针实时荧光PCR方法及其引物探针组合 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001256305A (ja) * | 2000-03-13 | 2001-09-21 | Kazutoshi Mogi | 遺伝子検査データ活用方法 |
JP2002024385A (ja) * | 2000-06-30 | 2002-01-25 | Coreflow Technologies:Kk | 遺伝子情報管理システム及びその管理方法 |
WO2002025519A1 (fr) * | 2000-09-20 | 2002-03-28 | Kabushiki Kaisha Toshiba | Procede visant a fournir une information de diagnostic a base de genes, terminal fournissant l'information, et terminal de reception de l'information |
JP2002197189A (ja) * | 2000-12-26 | 2002-07-12 | Sanyo Electric Co Ltd | 薬品テーラーメイドシステム |
JP2002245171A (ja) * | 2001-02-13 | 2002-08-30 | Canon Sales Co Inc | 医療情報管理装置、その方法、プログラム、記憶媒体 |
JP2002318858A (ja) * | 2001-04-19 | 2002-10-31 | Toshitada Kameda | 医療計画作成支援システム及びコンピュータプログラム |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5252743A (en) | 1989-11-13 | 1993-10-12 | Affymax Technologies N.V. | Spatially-addressable immobilization of anti-ligands on surfaces |
US5833599A (en) | 1993-12-13 | 1998-11-10 | Multum Information Services | Providing patient-specific drug information |
CA2267070A1 (en) | 1996-11-06 | 1998-05-14 | Sequenom, Inc. | Compositions and methods for immobilizing nucleic acids to solid supports |
US20020010595A1 (en) * | 1998-02-27 | 2002-01-24 | Kapp Thomas L. | Web-based medication management system |
IL138620A0 (en) * | 1998-04-03 | 2001-10-31 | Triangle Pharmaceuticals Inc | Systems, methods and computer program products for guiding the selection of therapeutic treatment regimens |
US6183963B1 (en) * | 1998-10-23 | 2001-02-06 | Signalgene | Detection of CYP1A1, CYP3A4, CYP2D6 and NAT2 variants by PCR-allele-specific oligonucleotide (ASO) assay |
JP2003516111A (ja) | 1999-02-22 | 2003-05-13 | バリアジェニックス インコーポレーテッド | 疾病の治療法の決定において有用性を有する遺伝子配列変異 |
US20010034023A1 (en) * | 1999-04-26 | 2001-10-25 | Stanton Vincent P. | Gene sequence variations with utility in determining the treatment of disease, in genes relating to drug processing |
US6297014B1 (en) * | 1999-07-02 | 2001-10-02 | Cedars-Sinai Medical Center | Genetic test to determine non-responsiveness to statin drug treatment |
US20020012921A1 (en) * | 2000-01-21 | 2002-01-31 | Stanton Vincent P. | Identification of genetic components of drug response |
US7206699B2 (en) * | 2000-04-18 | 2007-04-17 | Virco N.V. | Methods for measuring therapy resistance |
US20020010552A1 (en) * | 2000-05-26 | 2002-01-24 | Hugh Rienhoff | System for genetically characterizing an individual for evaluation using genetic and phenotypic variation over a wide area network |
US20020076774A1 (en) * | 2000-06-21 | 2002-06-20 | Chunhua Yan | Isolated human drug-metabolizing proteins, nucleic acid molecules encoding human drug-metabolizing proteins, and uses thereof |
AU2001278599A1 (en) | 2000-08-10 | 2002-02-18 | Glaxo Group Limited | A global electronic medicine response profile testing network |
US6812339B1 (en) * | 2000-09-08 | 2004-11-02 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
AU2001275020A1 (en) * | 2000-09-21 | 2002-04-02 | Theradoc.Com, Inc. | Systems and methods for manipulating medical data via a decision support system |
US6450956B1 (en) | 2000-11-06 | 2002-09-17 | Siemens Corporate Research, Inc. | System and method for treatment and outcome measurement analysis |
AU2002244568A1 (en) * | 2001-03-14 | 2002-09-24 | Mcgill University | Individualization of therapy with antipsychotics |
US20020187483A1 (en) * | 2001-04-20 | 2002-12-12 | Cerner Corporation | Computer system for providing information about the risk of an atypical clinical event based upon genetic information |
WO2003008637A2 (en) | 2001-07-17 | 2003-01-30 | Xanthus Life Sciences, Inc. | Use of genotyping in the individualization of therapy |
US7529685B2 (en) * | 2001-08-28 | 2009-05-05 | Md Datacor, Inc. | System, method, and apparatus for storing, retrieving, and integrating clinical, diagnostic, genomic, and therapeutic data |
US7461006B2 (en) * | 2001-08-29 | 2008-12-02 | Victor Gogolak | Method and system for the analysis and association of patient-specific and population-based genomic data with drug safety adverse event data |
US20030105596A1 (en) | 2001-10-29 | 2003-06-05 | Goldstein David Benjamin | Methods for evaluating responses of a group of test subjects to a drug or other clinical treatment and for predicting responses in other subjects |
WO2003039234A2 (en) * | 2001-11-06 | 2003-05-15 | David Pickar | Pharmacogenomics-based system for clinical applications |
US20030157110A1 (en) * | 2002-01-07 | 2003-08-21 | Millennium Pharmaceuticals, Inc. | Methods for the treatment of metabolic disorders, including obesity and diabetes |
US7274707B2 (en) * | 2002-03-07 | 2007-09-25 | Koninklijke Philips Electronics N. V. | Coexistence of stations capable of different modulation schemes in a wireless local area network |
US20030204415A1 (en) * | 2002-04-30 | 2003-10-30 | Calvin Knowlton | Medical data and medication selection and distribution system |
US7809585B1 (en) | 2002-06-12 | 2010-10-05 | Anvita, Inc. | System and method for patient-specific optimization of medical therapy by simultaneous symbolic reasoning in all clinical dimensions |
EP2393028B1 (en) | 2003-02-20 | 2015-09-30 | Mayo Foundation For Medical Education And Research | Methods for selecting antidepressant medications |
US8688385B2 (en) | 2003-02-20 | 2014-04-01 | Mayo Foundation For Medical Education And Research | Methods for selecting initial doses of psychotropic medications based on a CYP2D6 genotype |
US20040193446A1 (en) | 2003-03-27 | 2004-09-30 | Mayer Steven Lloyd | System and method for managing a patient treatment program including a prescribed drug regimen |
US20050069936A1 (en) | 2003-09-26 | 2005-03-31 | Cornelius Diamond | Diagnostic markers of depression treatment and methods of use thereof |
WO2005038049A2 (en) | 2003-10-06 | 2005-04-28 | Heinrich Guenther | System and method for optimizing drug therapy |
US7813880B2 (en) | 2004-03-25 | 2010-10-12 | University Of Maryland, Baltimore | Apparatus and method for providing optimal concentrations for medication infusions |
EP1751673A4 (en) | 2004-05-03 | 2008-06-25 | Cygene Lab Inc | PROCESS AND SYSTEM FOR COMPREHENSIVE, KNOWLEDGE BASED ANONYMOUS TESTS AND REPORTS AND FOR THE PROVISION OF SELECTIVE ACCESS TO RESULTS AND REPORTS |
US20050260549A1 (en) | 2004-05-19 | 2005-11-24 | Feierstein Roslyn E | Method of analyzing question responses to select among defined possibilities and means of accomplishing same |
US7546285B1 (en) | 2004-09-24 | 2009-06-09 | Sprint Communications Company L.P. | System and method for scoring development concepts |
AU2005319028B2 (en) | 2004-12-21 | 2010-09-16 | Academia Sinica | Genetic variants of VKORCI predicting warfarin sensitivity |
WO2006075254A2 (en) | 2005-01-13 | 2006-07-20 | Progenika Biopharma, S.A. | Methods and products for in vitro genotyping |
EP1906973A2 (en) | 2005-06-14 | 2008-04-09 | Baxter International Inc. | Pharmaceutical formulations for minimizing drug-drug interactions |
FR2887663A1 (fr) * | 2005-06-24 | 2006-12-29 | Ippm Holding Sa | Procede et systeme d'information pour generer des donnees d'optimisation d'un traitement medical, et equipement mis en oeuvre dans ce systeme |
AU2006320633A1 (en) | 2005-11-29 | 2007-06-07 | Children's Hospital Medical Center | Optimization and individualization of medication selection and dosing |
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- 2013-03-11 US US13/792,365 patent/US20130311202A1/en not_active Abandoned
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- 2015-01-30 US US14/610,941 patent/US9111028B2/en not_active Expired - Lifetime
- 2015-11-13 US US14/940,375 patent/US20160237494A1/en not_active Abandoned
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- 2019-05-15 US US16/413,125 patent/US20200048712A1/en not_active Abandoned
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001256305A (ja) * | 2000-03-13 | 2001-09-21 | Kazutoshi Mogi | 遺伝子検査データ活用方法 |
JP2002024385A (ja) * | 2000-06-30 | 2002-01-25 | Coreflow Technologies:Kk | 遺伝子情報管理システム及びその管理方法 |
WO2002025519A1 (fr) * | 2000-09-20 | 2002-03-28 | Kabushiki Kaisha Toshiba | Procede visant a fournir une information de diagnostic a base de genes, terminal fournissant l'information, et terminal de reception de l'information |
JP2002197189A (ja) * | 2000-12-26 | 2002-07-12 | Sanyo Electric Co Ltd | 薬品テーラーメイドシステム |
JP2002245171A (ja) * | 2001-02-13 | 2002-08-30 | Canon Sales Co Inc | 医療情報管理装置、その方法、プログラム、記憶媒体 |
JP2002318858A (ja) * | 2001-04-19 | 2002-10-31 | Toshitada Kameda | 医療計画作成支援システム及びコンピュータプログラム |
Non-Patent Citations (2)
Title |
---|
JPN6009052752; Am.J.Pharmacogenomics,Vol.1,No.1(2001)p.3-10 * |
JPN6009052754; Exp.Rev.Mol.Diagn.,Vol.1,No.3(2001)p.275-280 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011154800A (ja) * | 2010-01-26 | 2011-08-11 | Sumitomo Chemical Co Ltd | 発光装置およびその製造方法 |
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US9111028B2 (en) | 2015-08-18 |
EP2393028A2 (en) | 2011-12-07 |
JP5348840B2 (ja) | 2013-11-20 |
US20150148336A1 (en) | 2015-05-28 |
WO2004074456A3 (en) | 2006-07-27 |
EP2393028A3 (en) | 2012-02-29 |
US20070003931A1 (en) | 2007-01-04 |
HK1164503A1 (en) | 2012-09-21 |
JP5438610B2 (ja) | 2014-03-12 |
EP1599576A4 (en) | 2008-02-13 |
DK1599576T3 (en) | 2016-08-01 |
EP2393028B1 (en) | 2015-09-30 |
EP1599576B1 (en) | 2016-04-27 |
ES2557885T3 (es) | 2016-01-29 |
US20230420139A1 (en) | 2023-12-28 |
ES2575903T3 (es) | 2016-07-04 |
US20130311202A1 (en) | 2013-11-21 |
US8401801B2 (en) | 2013-03-19 |
DK2393028T3 (en) | 2016-01-11 |
US20200048712A1 (en) | 2020-02-13 |
JP5438524B2 (ja) | 2014-03-12 |
US20160237494A1 (en) | 2016-08-18 |
WO2004074456A2 (en) | 2004-09-02 |
JP2007525154A (ja) | 2007-09-06 |
EP1599576A2 (en) | 2005-11-30 |
JP2010273681A (ja) | 2010-12-09 |
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