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1. 发明申请

US20060008851A1 Methods for rapid and quantitative proteome analysis 审中-公开
公开(公告)号：US20060008851A1
公开(公告)日：2006-01-12
申请号：US11223269
申请日：2005-09-09
申请人： Rudolf Aebersold , David Goodlett
发明人： Rudolf Aebersold , David Goodlett
IPC分类号： G01N33/53
CPC分类号： G01N33/6803
摘要： The invention provides methods for identifying a polypeptide. The method can include determining two or more characteristics associated with the polypeptide, or a fragment thereof, one of the characteristics being mass of a fragment of the polypeptide, the fragment mass being determined by mass spectrometry; comparing the characteristics associated with the polypeptide to an annotated polypeptide index; and identifying one or more polypeptides in the annotated polypeptide index having the characteristics. The method can further include the steps of determining one or more additional characteristics associated with the polypeptide; comparing the determined characteristics to the annotated polypeptide index; optionally repeating the steps one or more times, wherein a set of characteristics is determined that identifies a single polypeptide in the annotated polypeptide index, and optionally quantitating the amount of identified polypeptide in a sample containing the polypeptide. The invention also provides methods for generating a polypeptide identification index.

2. 发明授权

US08501421B2 Method for high throughput peptide/protein assay generation and assays generated therewith 有权
标题翻译：用于生成高通量肽/蛋白质测定法的方法和由此产生的测定法
公开(公告)号：US08501421B2
公开(公告)日：2013-08-06
申请号：US12994093
申请日：2009-05-20
申请人： Rudolf Aebersold , Paola Picotti , Oliver Rinner , Johan Malmstroem
发明人： Rudolf Aebersold , Paola Picotti , Oliver Rinner , Johan Malmstroem
IPC分类号： G01N31/00 , G01N33/53
CPC分类号： G01N33/6848
摘要： The invention relates to a method for the determination of an MRM or SRM assay for a protein of interest, a peptide of interest, or a group of proteins/peptides of interest or a whole proteome. It essentially includes the following steps: (1) a list of proteins of interest is selected and for each member at least one or a list of candidate proteotypic peptides is derived (2) this at least one peptide is synthesized/generated essentially without subsequent purification; (3) this at least one unpurified peptide is analyzed by selected reaction monitoring (SRM) preferably coupled to liquid chromatography (LC-SRM) or analogous techniques; (4) validation and/or optimisation of the corresponding assay of the at least one peptide with determination of the SRM coordinates for a peptide/protein of interest and/or of a regulator of interest is achieved. A protein sample of interest is enzymatically digested and can then be analyzed in SRM mode or time-constrained SRM mode, using elution times to trigger acquisition of the set of selected SRM traces, thus drastically increasing the throughput. The analysis allows to detect and quantify the set of peptides/proteins of interest. The method additionally relates to a tagging strategy to achieve absolute quantification of the peptides/proteins of interest at low-budget and high-throughput.
摘要翻译：本发明涉及用于确定感兴趣的蛋白质，目标肽或感兴趣的蛋白质/肽组或整个蛋白质组的MRM或SRM测定法的方法。它基本上包括以下步骤：（1）选择目的蛋白的列表，并且对于每个成员，导出候选蛋白多肽的至少一个或一个或多个列表（2）该基因上没有随后的纯化合成/生成至少一种肽 ; （3）通过优选与液相色谱法（LC-SRM）偶联的选择性反应监测（SRM）或类似技术来分析至少一种未纯化的肽。（4）通过确定感兴趣的肽/ /蛋白质和/或感兴趣的调节剂的SRM坐标来确定和/或优化至少一种肽的相应测定。感兴趣的蛋白质样品被酶消化，然后可以以SRM模式或时间受限的SRM模式进行分析，使用洗脱时间来触发所选择的SRM迹线的采集，从而大大增加产量。该分析允许检测和定量所组合的肽/蛋白质。该方法另外涉及在低预算和高通量下实现目标肽/蛋白质的绝对定量的标记策略。

3. 发明申请

US20110065605A1 METHOD FOR BIOMARKER AND DRUG-TARGET DISCOVERY FOR PROSTATE CANCER DIAGNOSIS AND TREATMENT AS WELL AS BIOMARKER ASSAYS DETERMINED THEREWITH 审中-公开
公开(公告)号：US20110065605A1
公开(公告)日：2011-03-17
申请号：US12992542
申请日：2009-05-12
申请人： Wilhelm Krek , Igor Cima , Rudolf Aebersold , Ralph Schiess , Thomas Cerny , Silke Gillessen
发明人： Wilhelm Krek , Igor Cima , Rudolf Aebersold , Ralph Schiess , Thomas Cerny , Silke Gillessen
IPC分类号： C40B30/04 , G01N33/566 , G01N33/68 , C12Q1/37 , H01J49/26
CPC分类号： G01N33/57434 , G01N33/57407 , G01N33/6848 , G01N2333/47 , G01N2333/70525 , G01N2333/8146
摘要： The invention relates to a method for the determination of a cancer diagnostic/therapeutic biomarker assay and drug-targets including the following steps: (a) identification of potential candidate protein/peptide biomarkers and drug-targets based on the measurement of protein/peptide constituent concentrations in tissue sample proteomes as well as serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy non-human mammalian individuals as well as from cancerous non-human mammalian individuals and qualitatively selecting as potential candidate protein/peptide biomarkers those which show a pronounced differential behaviour between healthy and cancerous sample proteomes; (b) optional verification of the potential candidate protein/peptide biomarkers as identified in step (a) by quantitative mass spectrometric measurement of the potential candidate protein biomarkers in serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy non-human mammalian individuals as well as from cancerous non-human mammalian individuals and selecting as candidate protein/peptide biomarkers those which show a mass-spectrometrically measurable quantitative differential behaviour between healthy and cancerous sample proteomes; (c) validation of the candidate protein/peptide biomarkers as identified in step (a), or as optionally verified in step (b), by mass spectrometric measurement and/or antibody-based assays such as an Enzyme-Linked Immunosorbent Assay (ELISA) determination of the candidate protein biomarkers in serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy human individuals as well as from cancerous human individuals and selecting as protein/peptide biomarkers those which show a mass-spectrometrically measurable and/or antibody-based assay detectable differential behaviour between healthy and cancerous sample proteomes; (d) application of statistical methods to uncover single or groups of protein/peptide biomarkers as validated in step (c) as signatures for the detection of patients with cancer. The invention furthermore relates to specific biomarker assays for the highly reliable diagnosis of cancer, specifically of localized or non-localized prostate cancer, using human serum, plasma or any other derivatives of blood, or blood itself.

4. 发明申请

US20130206979A1 Data Independent Acquisition of Product Ion Spectra and Reference Spectra Library Matching 有权
公开(公告)号：US20130206979A1
公开(公告)日：2013-08-15
申请号：US13819769
申请日：2011-09-14
申请人： Ronald F. Bonner , Stephen A. Tate , Rudolf Aebersold , Pedro Jose Navarro ALvarez , Oliver Rinner , Lukas Reiter , Ludovic Gillet
发明人： Ronald F. Bonner , Stephen A. Tate , Rudolf Aebersold , Pedro Jose Navarro ALvarez , Oliver Rinner , Lukas Reiter , Ludovic Gillet
IPC分类号： H01J49/00
CPC分类号： H01J49/0036 , G01N30/7233 , G06F19/703 , G06F19/709 , H01J49/0031 , H01J49/004 , H01J49/0045 , H01J49/42
摘要： Systems and methods are used to store an electronic record of all product ion spectra of all detectable compounds of a sample. A plurality of product ion scans are performed on a tandem mass spectrometer one or more times in a single sample analysis across a mass range using a plurality of mass selection windows. All sample product ion spectra of all detectable compounds for each mass selection window are produced. All sample product ion spectra for each mass selection window are received from the tandem mass spectrometer using a processor. All sample product ion spectra for each mass selection window are stored as an electronic record of all detectable compounds of the sample using the processor. The electronic record is used to characterize compounds known at the time the electronic record is stored or to characterize compounds that became known after the electronic record was stored.

5. 发明申请

US20050233399A1 Rapid quantitative analysis of proteins or protein function in complex mixtures 有权
公开(公告)号：US20050233399A1
公开(公告)日：2005-10-20
申请号：US10994815
申请日：2004-11-23
申请人： Rudolf Aebersold , Michael Gelb , Steven Gygi , C. Scott , Frantisek Turecek , Scott Gerber , Beate Rist
发明人： Rudolf Aebersold , Michael Gelb , Steven Gygi , C. Scott , Frantisek Turecek , Scott Gerber , Beate Rist
IPC分类号： G01N27/62 , C12Q1/25 , C12Q1/34 , C12Q1/48 , G01N30/00 , G01N30/06 , G01N30/60 , G01N30/72 , G01N30/88 , G01N33/53 , G01N33/566 , G01N33/58 , G01N33/68
CPC分类号： G01N33/6848 , C12Q1/25 , G01N33/58 , G01N33/6803 , G01N33/6842 , Y10S530/812 , Y10T436/182 , Y10T436/24 , Y10T436/25 , Y10T436/25125 , Y10T436/25375
摘要： Analytical reagents and mass spectrometry-based methods using these reagents for the rapid, and quantitative analysis of proteins or protein function in mixtures of proteins. The methods employ affinity labeled protein reactive reagents having three portions: an affinity label (A) covalently linked to a protein reactive group (PRG) through a linker group (L). The linker may be differentially isotopically labeled, e.g., by substitution of one or more atoms in the linker with a stable isotope thereof. These reagents allow for the selective isolation of peptide fragments or the products of reaction with a given protein (e.g., products of enzymatic reaction) from complex mixtures. The isolated peptide fragments or reaction products are characteristic of the presence of a protein or the presence of a protein function in those mixtures. Isolated peptides or reaction products are characterized by mass spectrometric (MS) techniques. The reagents also provide for differential isotopic labeling of the isolated peptides or reaction products which facilitates quantitative determination by mass spectrometry of the relative amounts of proteins in different samples. The methods of this invention can be used for qualitative and quantitative analysis of global protein expression profiles in cells and tissues, to screen for and identify proteins whose expression level in cells, tissue or biological fluids is affected by a stimulus or by a change in condition or state of the cell, tissue or organism from which the sample originated.

6. 发明授权

US08324347B2 Methods of using halogenated peptides as internal standards for liquid chromatography-mass spectrometry 有权
标题翻译：使用卤化肽作为液相色谱 - 质谱法的内部标准的方法
公开(公告)号：US08324347B2
公开(公告)日：2012-12-04
申请号：US12707137
申请日：2010-02-17
申请人： Hamid Mirzaei , Rudolf Aebersold
发明人： Hamid Mirzaei , Rudolf Aebersold
IPC分类号： A61K38/04 , C07K5/00 , C07K7/00 , C07K16/00 , C07K17/00
CPC分类号： H01J49/0009 , C07K5/1016 , C07K7/06 , C07K7/08 , G01N33/6848 , G01N2496/00 , H01J49/0036 , Y10T436/105831
摘要： Methods of using halogenated peptides as internal standards for liquid chromatography-mass spectrometry, and novel halogenated peptides useful for the same, are disclosed. In particular, methods of using halogenated peptides as internal standards in proteomic analyses, as well as methods of using halogenated peptides to conduct quality control assessments of and/or to calibrate liquid chromatography-mass spectrometry systems are disclosed.
摘要翻译：公开了使用卤化肽作为液相色谱 - 质谱法的内部标准的方法和可用于其的新型卤代肽。特别地，公开了在蛋白质组学分析中使用卤化肽作为内部标准的方法，以及使用卤化肽进行液体色谱 - 质谱系统的质量控制评估和/或校准的方法。

7. 发明申请

US20070202539A1 Methods for quantitative proteome analysis of glycoproteins 审中-公开
公开(公告)号：US20070202539A1
公开(公告)日：2007-08-30
申请号：US11655614
申请日：2007-01-18
申请人： Rudolf Aebersold , Hui Zhang
发明人： Rudolf Aebersold , Hui Zhang
IPC分类号： G01N33/53 , C12Q1/37 , C07K14/47
CPC分类号： G01N33/6848 , C12Q1/34 , C12Q1/37 , G01N33/68 , G01N33/6803 , G01N33/6842 , G01N33/6851 , G01N2400/00 , G01N2458/15 , Y10T436/24 , Y10T436/25125
摘要： The invention provides a method for identifying and quantifying polyglycopeptides in a sample. The method can include the steps of immobilizing glycopolypeptides to a solid support; cleaving the immobilized glycopolypeptides, thereby releasing non-glycosylated peptides and retaining immobilized glycopeptides; releasing the glycopeptides from the solid support; and analyzing the released glycopeptides. The method can further include the step of identifying one or more glycopeptides, for example, using mass spectrometry.

8. 发明申请

US20070099251A1 Tissue-and serum-derived glycoproteins and methods of their use 审中-公开
标题翻译：组织和血清来源的糖蛋白及其使用方法
公开(公告)号：US20070099251A1
公开(公告)日：2007-05-03
申请号：US11582861
申请日：2006-10-17
申请人： Hui Zhang , Rudolf Aebersold
发明人： Hui Zhang , Rudolf Aebersold
IPC分类号： G01N33/574 , C12M3/00
CPC分类号： G01N33/574 , G01N33/6848 , G01N2800/00 , G01N2800/342 , G01N2800/52
摘要： The present invention is directed generally to tissue-derived glycoproteins and glycosites detectable in plasma via mass spectrometric analysis of glycoproteins from both tissues and blood. The invention also provides methods for identifying tissue-derived glycoproteins and glycosites in plasma, panels of detection reagents for detecting same, as well methods for detecting disease using such panels. The invention further provides a database of tissue-derived glycoproteins and glycosites detectable in plasma.
摘要翻译：本发明一般涉及通过来自组织和血液的糖蛋白的质谱分析在血浆中可检测的组织衍生的糖蛋白和糖皮质激素。本发明还提供了用于鉴定血浆中组织衍生的糖蛋白和糖原的方法，用于检测血浆的检测试剂盒，以及用于使用这种面板检测疾病的方法。本发明还提供了可在血浆中检测的组织衍生的糖蛋白和糖原的数据库。

9. 发明申请

US20080108152A1 Methods for characterizing glycoproteins and generating antibodies for same 有权
标题翻译：表征糖蛋白并产生相同抗体的方法
公开(公告)号：US20080108152A1
公开(公告)日：2008-05-08
申请号：US11891487
申请日：2007-08-09
申请人： Dan Martin , Bernd Wollscheid , Rudolf Aebersold , Julian Watts
发明人： Dan Martin , Bernd Wollscheid , Rudolf Aebersold , Julian Watts
IPC分类号： C07K16/18
CPC分类号： C07K16/28
摘要： The invention provides methods for generating an antibody specific for the deglycosylated form of a glycopolypeptide using a peptide corresponding to an N-linked glycosylation site of a glycopolypeptide. The invention additionally provides methods for generating an antibody specific for a glycopolypeptide using a peptide corresponding to amino acids adjacent to an authentic N-linked glycosylation site.
摘要翻译：本发明提供使用对应于糖多肽的N-连接糖基化位点的肽产生对糖多糖形式的去糖基化形式特异的抗体的方法。本发明另外提供了使用对应于与真实N-连接的糖基化位点相邻的氨基酸的肽来产生对糖多肽特异性的抗体的方法。

10. 发明申请

US20070269895A1 Methods for quantitative proteome analysis of glycoproteins 审中-公开
公开(公告)号：US20070269895A1
公开(公告)日：2007-11-22
申请号：US11586485
申请日：2006-10-24
申请人： Rudolf Aebersold , Hui Zhang , Leroy Hood , Bingyun Sun
发明人： Rudolf Aebersold , Hui Zhang , Leroy Hood , Bingyun Sun
IPC分类号： G01N33/00 , G01N33/53 , G01N37/00
CPC分类号： C12Q1/34 , C12Q1/37 , G01N33/68 , G01N33/6803 , G01N33/6842 , G01N33/6848 , G01N33/6851 , Y10T436/13
摘要： The invention provides a method for identifying and quantifying polyglycopeptides in a sample. The method can include the steps of immobilizing glycopolypeptides to a solid support; cleaving the immobilized glycopolypeptides, thereby releasing non-glycosylated peptides and retaining immobilized glycopeptides; releasing the glycopeptides from the solid support; and analyzing the released glycopeptides. The method can further include the step of identifying one or more glycopeptides, for example, using mass spectrometry.

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