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公开(公告)号：US09619624B2
公开(公告)日：2017-04-11
申请号：US14849211
申请日：2015-09-09
CPC分类号： G06F19/345 , G06F19/00 , G06F19/18 , G06F19/326 , G06F19/3437 , G16H50/20 , G16H50/50
摘要： The present disclosure is directed to systems and methods for identifying unknown drug targets via adverse event data. An analyzer receives an identification of a first drug having one or more unknown target proteins and identifies a second drug related to the first drug. The analyzer retrieves, from an adverse event database, a first side effect profile associated with the first drug, and a second side effect profile associated with the second drug. The analyzer generates a third side effect profile comprising a subset of the first side effect profile not shared by the second side effect profile, and identifies a third drug having a fourth side effect profile comprising the third side effect profile. The analyzer retrieves a list of one or more target proteins of the third drug not targeted by the second drug, and presents the retrieved list as potential target proteins of the first drug.
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2.发明授权Systems and methods for using adverse event data to predict potential side effects 有权使用不良事件数据预测潜在副作用的系统和方法公开(公告)号：US09235686B2
公开(公告)日：2016-01-12
申请号：US13446912
申请日：2012-04-13
CPC分类号： G06F19/345 , G06F19/00 , G06F19/18 , G06F19/326 , G06F19/3437 , G16H50/20 , G16H50/50
摘要： The present disclosure describes systems and methods for predicting a likely side effect profile for even new, untested medications. A predicted side effect profile may be generated based on intersections of side effect profiles of other medications that affect the same or related molecular entities, such as the nearby target proteins, involve the same pathways, or are otherwise similarly related. To generate a predicted side effect profile for a new drug targeting a novel or previously un-targeted protein target, an analyzer may query an adverse event database for records pertaining to patients who have taken drugs or combinations of drugs that target or affect molecular entities in the vicinity of the novel target within a global molecular entity graph, and, in some embodiments, may retrieve a plurality of adverse event records and generate an intersection of side effects associated with related targets to predict likely side effects for the novel target.
摘要翻译： 本公开描述了用于预测甚至新的未经检验的药物的可能的副作用特征的系统和方法。 可以基于影响相同或相关分子实体的其它药物（例如附近靶蛋白，涉及相同途径）的副作用分布的交叉点或者以其他方式相似的方式产生预测的副作用分布。 为了产生针对新颖或先前未靶向的蛋白质靶标的新药物的预测副作用特征，分析器可以查询不良事件数据库以获得关于已经服用药物或靶向或影响分子实体的药物组合的患者的记录 在全局分子实体图中的新靶标的附近，并且在一些实施例中，可以检索多个不利事件记录并产生与相关目标相关联的副作用的交集，以预测新颖目标的可能副作用。
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公开(公告)号：US10672514B2
公开(公告)日：2020-06-02
申请号：US14763027
申请日：2013-10-01
发明人： Alexander Zien , David B. Jackson , Martin Stein , Guillaume Taglang , Stephan Brock , Alexander Picker , Theodoros Soldatos , Bernhard Sulzer
摘要： The present disclosure relates to systems and methods for bioinformatics and data processing. In particular, in a first aspect, the present disclosure relates to methods and systems for generating a personalized treatment guideline for a patient and for selecting a treatment for a patient. In another aspect, the present disclosure relates to methods and systems for selecting patients for a clinical trial of a treatment. The invention resolves cases in which patients have more than one “actionable” aberration by combining the patient-specific molecular information and the treatment-specific molecular information further with a clinico-molecular disease model, specifically a scoring of genes and/or proteins that represents several aspects of their involvement into the disease. In this way, treatments and patients can be prioritized that are most likely to impact or impacted by the disease mechanism, respectively.
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4.发明申请NOVEL TISSUE PROTECTIVE ERYTHROPOIETIN RECEPTOR (NEPOR) AND METHODS OF USE 审中-公开新型组织保护性ERYTHROPOIETIN受体（NEPOR）及其使用方法公开(公告)号：US20140296318A1
公开(公告)日：2014-10-02
申请号：US14060027
申请日：2013-10-22
发明人： DAVID B. JACKSON , MARTIN STEIN , HARTMUT VOSS , STEPHAN BROCK , CHRISTOPHER G. DANES , ANIL SOOD
IPC分类号： G01N33/574 , C12N15/113 , C12Q1/68
CPC分类号： G01N33/57492 , C12N15/1138 , C12Q1/6886 , C12Q2600/106 , G01N33/5011 , G01N33/5041 , G01N33/57415 , G01N33/746 , G01N2800/52
摘要： Methods of determining whether a patient is suitable for erythropoietin (EPO) therapy, including (A) isolating a tissue sample from said patient; (B) determining the level of expression of EPH-B4 in said sample; and (C) correlating a presence of EPH-B4 expression to a negative physiological response to EPO therapy). In addition, methods of enhancing the effectiveness of EPO therapy in a patient by administering to said patient, in conjunction with EPO therapy, an siRNA specific for EPH-B4.
摘要翻译： 确定患者是否适合促红细胞生成素（EPO）治疗的方法，包括（A）从所述患者分离组织样品; （B）确定所述样品中EPH-B4的表达水平; 和（C）将EPH-B4表达的存在与对EPO治疗的负面生理反应相关）。 另外，通过与EPO治疗一起向所述患者施用特异于EPH-B4的siRNA，来增强患者中EPO治疗的有效性的方法。
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5.发明授权公开(公告)号：US08357501B2
公开(公告)日：2013-01-22
申请号：US12474017
申请日：2009-05-28
申请人： David B. Jackson , Martin Stein , Hartmut Voss , Stephan Brock
发明人： David B. Jackson , Martin Stein , Hartmut Voss , Stephan Brock
IPC分类号： G01N33/53 , G01N33/15 , G01N33/48 , A61K38/18 , C07K14/505
CPC分类号： G01N33/57492 , C12N15/1138 , C12Q1/6886 , C12Q2600/106 , G01N33/5011 , G01N33/5041 , G01N33/57415 , G01N33/746 , G01N2800/52
摘要： There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumor allows EPO to impinge on the survival of associated cells thereby enhancing tumor progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumor as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin. Furthermore, by disclosing the molecular compositions of NEPOR species, there are disclosed methods for rationally identifying/designing NEPOR modulating therapeutics. Methods also are provided for treating neurological insults such as stroke (via enhancement of NEPOR activity) and cancer (via down-regulation of cyto-protective signaling from NEPOR).
摘要翻译： 公开了一种称为NEPOR的新型组织保护促红细胞生成素（EPO）结合受体蛋白复合物的分子组成。 在肿瘤上存在NEPOR成分允许EPO影响相关细胞的存活，从而增强肿瘤进展并对患者的存活产生负面影响。 NEPOR的存在代表较差的患者结局的预后生物标志物。 因此，提供了用于对具有适合的肿瘤（即NEPOR不存在）或不适合（即存在的NEPOR）用于EPO治疗的患者进行分层的方法，包括：（a）从正在接受或正在接受的个体分离组织样品 接受促红细胞生成素的候选物，（b）从分离的组织中确定NEPOR基因（mRNA）的表达水平和/或NEPOR基因产物（蛋白质）的存在，和（c） NEPOR基因表达产物或NEPOR蛋白的存在对促红细胞生成素治疗的生理反应。 此外，通过公开NEPOR种类的分子组成，公开了合理鉴定/设计NEPOR调节治疗剂的方法。 还提供用于治疗诸如中风（通过增强NEPOR活性）和癌症（通过NEPOR的细胞保护信号的下调）的神经学损伤的方法。
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公开(公告)号：US20170315128A1
公开(公告)日：2017-11-02
申请号：US15375447
申请日：2016-12-12
发明人： David B. Jackson , Martin Stein , Hartmut Voss , Stephan Brock
IPC分类号： G01N33/574 , C12Q1/68 , G01N33/50 , C12N15/113 , G01N33/74
CPC分类号： G01N33/57492 , C12N15/1138 , C12Q1/6886 , C12Q2600/106 , G01N33/5011 , G01N33/5041 , G01N33/57415 , G01N33/746 , G01N2800/52
摘要： There is disclosed a molecular composition(s) of a novel tissue protective erythropoietin (EPO) binding receptor protein complex, termed NEPOR. Presence of NEPOR components on a tumour allows EPO to impinge on the survival of associated cells thereby enhancing tumour progression and negatively effecting patient survival. Presence of NEPOR represents a prognostic biomarker for poorer patient outcome. Thus, methods are provided for stratifying patients having a tumour as suitable (i.e. NEPOR not present) or non-suitable (i.e., NEPOR present) for EPO treatment, comprising: (a) isolating a tissue sample from an individual who is receiving or is a candidate for receiving erythropoietin, (b) determining the level of expression of the NEPOR gene(s) (mRNA) and/or the presence of the NEPOR gene product (protein) from the isolated tissue, and (c) correlating the presence of an NEPOR gene expression product or the presence of NEPOR protein to a physiological response to the treatment with erythropoietin. Furthermore, by disclosing the molecular compositions of NEPOR species, there are disclosed methods for rationally identifying/designing NEPOR modulating therapeutics. Methods also are provided for treating neurological insults such as stroke (via enhancement of NEPOR activity) and cancer (via down-regulation of cyto-protective signaling from NEPOR).
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公开(公告)号：US09779214B2
公开(公告)日：2017-10-03
申请号：US13446917
申请日：2012-04-13
CPC分类号： G06F19/345 , G06F19/00 , G06F19/18 , G06F19/326 , G06F19/3437 , G16H50/20 , G16H50/50
摘要： The present disclosure describes systems and methods for using patient-specific genomic information to optimize or de-risk therapy for the patient. A user may identify a medication for consideration for prescription to a patient, and a genetic variant of the patient affecting a first protein. An analyzer may identify a second medication targeting the first protein, and may retrieve adverse event data from an adverse event database for patients co-medicated with both the first medication and second medication. The analyzer may determine, based on rates of adverse events, the likelihood of an adverse event occurring through co-medication of the first medication and second medication. Based on the likelihood, and based on a correspondence or non-correspondence between a protein activation characteristic of the first medication and the effect of the genetic variant of the patient, the analyzer may indicate or contra-indicate the first medication for the patient.
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8.发明授权Systems and methods for identifying unknown drug targets via adverse event data 有权通过不良事件数据识别未知药物靶标的系统和方法公开(公告)号：US09218457B2
公开(公告)日：2015-12-22
申请号：US13446871
申请日：2012-04-13
CPC分类号： G06F19/345 , G06F19/00 , G06F19/18 , G06F19/326 , G06F19/3437 , G16H50/20 , G16H50/50
摘要： The present disclosure is directed to systems and methods for identifying unknown drug targets via adverse event data. An analyzer receives an identification of a first drug having one or more unknown target proteins and identifies a second drug related to the first drug. The analyzer retrieves, from an adverse event database, a first side effect profile associated with the first drug, and a second side effect profile associated with the second drug. The analyzer generates a third side effect profile including a subset of the first side effect profile not shared by the second side effect profile, and identifies a third drug having a fourth side effect profile including the third side effect profile. The analyzer retrieves a list of one or more target proteins of the third drug not targeted by the second drug, and presents the retrieved list as potential target proteins of the first drug.
摘要翻译： 本公开涉及用于通过不良事件数据识别未知药物靶标的系统和方法。 分析仪接收具有一种或多种未知目标蛋白质的第一种药物的鉴定，并识别与第一种药物相关的第二种药物。 分析仪从不良事件数据库检索与第一药物相关联的第一副作用谱，以及与第二药物相关联的第二副作用谱。 分析仪产生包括第二副作用轮廓不共享的第一副作用轮廓的子集的第三副作用轮廓，并且识别具有包括第三副作用轮廓的第四副作用轮廓的第三药物。 分析仪检索第二种药物未靶向的第三种药物的一种或多种靶蛋白的列表，并将检索到的列表作为第一种药物的潜在靶蛋白。
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公开(公告)号：US20210202037A1
公开(公告)日：2021-07-01
申请号：US16724545
申请日：2019-12-23
发明人： Martin STEIN , Regina BOHNERT , Nora RIEBER
摘要： The present invention relates to a method for genomic and/or genetic analysis of a human nucleic acid sample, the method comprising the steps of providing a group of human reference genomes; testing of the human nucleic acid sample for sex and/or ancestry; selecting one or more population-specific human reference genomes, PHREGs, from the group of human reference genomes on the basis on the results of the sex and/or ancestry test; and aligning the human nucleic acid sample to the selected PHREGs; and variant calling against the selected PHREGs. The present invention also provides respective computer systems and computer programs.
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