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  1. Artikel ; Online: Joint evolutionary trees

    Stefan Engelen / Ladislas A Trojan / Sophie Sacquin-Mora / Richard Lavery / Alessandra Carbone

    PLoS Computational Biology, Vol 5, Iss 1, p e

    a large-scale method to predict protein interfaces based on sequence sampling.

    2009  Band 1000267

    Abstract: The Joint Evolutionary Trees (JET) method detects protein interfaces, the core residues involved in the folding process, and residues susceptible to site-directed mutagenesis and relevant to molecular recognition. The approach, based on the Evolutionary ... ...

    Abstract The Joint Evolutionary Trees (JET) method detects protein interfaces, the core residues involved in the folding process, and residues susceptible to site-directed mutagenesis and relevant to molecular recognition. The approach, based on the Evolutionary Trace (ET) method, introduces a novel way to treat evolutionary information. Families of homologous sequences are analyzed through a Gibbs-like sampling of distance trees to reduce effects of erroneous multiple alignment and impacts of weakly homologous sequences on distance tree construction. The sampling method makes sequence analysis more sensitive to functional and structural importance of individual residues by avoiding effects of the overrepresentation of highly homologous sequences and improves computational efficiency. A carefully designed clustering method is parametrized on the target structure to detect and extend patches on protein surfaces into predicted interaction sites. Clustering takes into account residues' physical-chemical properties as well as conservation. Large-scale application of JET requires the system to be adjustable for different datasets and to guarantee predictions even if the signal is low. Flexibility was achieved by a careful treatment of the number of retrieved sequences, the amino acid distance between sequences, and the selective thresholds for cluster identification. An iterative version of JET (iJET) that guarantees finding the most likely interface residues is proposed as the appropriate tool for large-scale predictions. Tests are carried out on the Huang database of 62 heterodimer, homodimer, and transient complexes and on 265 interfaces belonging to signal transduction proteins, enzymes, inhibitors, antibodies, antigens, and others. A specific set of proteins chosen for their special functional and structural properties illustrate JET behavior on a large variety of interactions covering proteins, ligands, DNA, and RNA. JET is compared at a large scale to ET and to Consurf, Rate4Site, siteFiNDER|3D, and SCORECONS on ...
    Schlagwörter Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 612
    Sprache Englisch
    Erscheinungsdatum 2009-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Joint evolutionary trees: a large-scale method to predict protein interfaces based on sequence sampling.

    Engelen, Stefan / Trojan, Ladislas A / Sacquin-Mora, Sophie / Lavery, Richard / Carbone, Alessandra

    PLoS computational biology

    2009  Band 5, Heft 1, Seite(n) e1000267

    Abstract: The Joint Evolutionary Trees (JET) method detects protein interfaces, the core residues involved in the folding process, and residues susceptible to site-directed mutagenesis and relevant to molecular recognition. The approach, based on the Evolutionary ... ...

    Abstract The Joint Evolutionary Trees (JET) method detects protein interfaces, the core residues involved in the folding process, and residues susceptible to site-directed mutagenesis and relevant to molecular recognition. The approach, based on the Evolutionary Trace (ET) method, introduces a novel way to treat evolutionary information. Families of homologous sequences are analyzed through a Gibbs-like sampling of distance trees to reduce effects of erroneous multiple alignment and impacts of weakly homologous sequences on distance tree construction. The sampling method makes sequence analysis more sensitive to functional and structural importance of individual residues by avoiding effects of the overrepresentation of highly homologous sequences and improves computational efficiency. A carefully designed clustering method is parametrized on the target structure to detect and extend patches on protein surfaces into predicted interaction sites. Clustering takes into account residues' physical-chemical properties as well as conservation. Large-scale application of JET requires the system to be adjustable for different datasets and to guarantee predictions even if the signal is low. Flexibility was achieved by a careful treatment of the number of retrieved sequences, the amino acid distance between sequences, and the selective thresholds for cluster identification. An iterative version of JET (iJET) that guarantees finding the most likely interface residues is proposed as the appropriate tool for large-scale predictions. Tests are carried out on the Huang database of 62 heterodimer, homodimer, and transient complexes and on 265 interfaces belonging to signal transduction proteins, enzymes, inhibitors, antibodies, antigens, and others. A specific set of proteins chosen for their special functional and structural properties illustrate JET behavior on a large variety of interactions covering proteins, ligands, DNA, and RNA. JET is compared at a large scale to ET and to Consurf, Rate4Site, siteFiNDER|3D, and SCORECONS on specific structures. A significant improvement in performance and computational efficiency is shown.
    Mesh-Begriff(e) Binding Sites/genetics ; Cluster Analysis ; Computational Biology/methods ; Conserved Sequence/genetics ; Databases, Protein ; Evolution, Molecular ; Models, Chemical ; Models, Molecular ; Neural Networks, Computer ; Phylogeny ; Protein Binding/genetics ; Protein Conformation ; Protein Interaction Mapping/methods ; Proteins/chemistry ; Proteins/genetics ; Proteins/metabolism ; Sequence Analysis, Protein/methods ; Sequence Homology, Amino Acid ; Structure-Activity Relationship
    Chemische Substanzen Proteins
    Sprache Englisch
    Erscheinungsdatum 2009-01-23
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1000267
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours

    Jerzy Trojan / Yuexin X. Pan / Ming X. Wei / Adama Ly / Alexander Shevelev / Maciej Bierwagen / Marie-Yvonne Ardourel / Ladislas A. Trojan / Alvaro Alvarez / Christian Andres / Maria C. Noguera / Ignacio Briceno / Beatriz H. Aristizabal / Heliodor Kasprzak / Huynh T. Duc / Donald D. Anthony

    Chemotherapy Research and Practice, Vol

    2012  Band 2012

    Schlagwörter Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R ; DOAJ:Therapeutics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Hindawi Publishing Corporation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Erratum to “Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours”

    Jerzy Trojan / Yuexin X. Pan / Ming X. Wei / Adama Ly / Alexander Shevelev / Maciej Bierwagen / Marie-Yvonne Ardourel / Ladislas A. Trojan / Alvaro Alvarez / Christian Andres / Maria C. Noguera / Ignacio Briceno / Beatriz H. Aristizabal / Heliodor Kasprzak / Huynh T. Duc / Donald D. Anthony

    Chemotherapy Research and Practice, Vol

    2012  Band 2012

    Schlagwörter Therapeutics. Pharmacology ; RM1-950 ; Medicine ; R ; DOAJ:Therapeutics ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Sprache Englisch
    Erscheinungsdatum 2012-01-01T00:00:00Z
    Verlag Hindawi Publishing Corporation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours.

    Trojan, Jerzy / Pan, Yuexin X / Wei, Ming X / Ly, Adama / Shevelev, Alexander / Bierwagen, Maciej / Ardourel, Marie-Yvonne / Trojan, Ladislas A / Alvarez, Alvaro / Andres, Christian / Noguera, Maria C / Briceno, Ignacio / Aristizabal, Beatriz H / Kasprzak, Heliodor / Duc, Huynh T / Anthony, Donald D

    Chemotherapy research and practice

    2012  Band 2012, Seite(n) 721873

    Abstract: The aim of this study was to establish the criteria for methodology of cellular "anti-IGF-I" therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and ... ...

    Abstract The aim of this study was to establish the criteria for methodology of cellular "anti-IGF-I" therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell "vaccines" should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8(+) and CD8(+)28(+) molecules and a switch from CD8(+)11b(+) to CD8(+)11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for "anti-IGF-I" strategy: characteristics sine qua non of injected "vaccines" (cloned cells IGF-I(-) and MHC-I(+)) and of PBL cells (CD8(+) increased level).
    Sprache Englisch
    Erscheinungsdatum 2012-02-14
    Erscheinungsland Egypt
    Dokumenttyp Journal Article
    ZDB-ID 2603560-1
    ISSN 2090-2115 ; 2090-2107
    ISSN (online) 2090-2115
    ISSN 2090-2107
    DOI 10.1155/2012/721873
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: IGF-I: from diagnostic to triple-helix gene therapy of solid tumors.

    Trojan, Ladislas A / Kopinski, Piotr / Wei, Ming X / Ly, Adama / Glogowska, Aleksandra / Czarny, Jolanta / Shevelev, Alexander / Przewlocki, Ryszard / Henin, Dominique / Trojan, Jerzy

    Acta biochimica Polonica

    2002  Band 49, Heft 4, Seite(n) 979–990

    Abstract: Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, ... ...

    Abstract Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.
    Mesh-Begriff(e) Apoptosis ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; Genetic Therapy ; Glioblastoma/diagnosis ; Glioblastoma/genetics ; Glioblastoma/immunology ; Glioblastoma/therapy ; Humans ; Insulin-Like Growth Factor I/analysis ; Insulin-Like Growth Factor I/antagonists & inhibitors ; Insulin-Like Growth Factor I/genetics ; Insulin-Like Growth Factor I/metabolism
    Chemische Substanzen Biomarkers, Tumor ; triplex DNA ; Insulin-Like Growth Factor I (67763-96-6) ; DNA (9007-49-2)
    Sprache Englisch
    Erscheinungsdatum 2002
    Erscheinungsland Poland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 595762-x
    ISSN 1734-154X ; 0001-527X
    ISSN (online) 1734-154X
    ISSN 0001-527X
    DOI 024904979
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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