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Article ; Online: A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against

NPJ vaccines

2020 Volume 5, Page(s) 75

Abstract: Leishmaniases are neglected diseases caused by infection ... ...

Abstract	Leishmaniases are neglected diseases caused by infection with
Language	English
Publishing date	2020-08-13
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-020-00224-0
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Article ; Online: The spatially resolved transcriptional profile of acute T cell-mediated rejection in a kidney allograft.

Salem, Fadi / Perin, Laura / Sedrakyan, Sargis / Angeletti, Andrea / Ghiggeri, Gian Marco / Coccia, Maria Cristina / Ross, Marty / Fribourg, Miguel / Cravedi, Paolo

Kidney international

2021 Volume 101, Issue 1, Page(s) 131–136

Abstract: ... T cell-mediated-rejection (TCMR), also known as acute cellular rejection. However, bulk RNA ... showed an enrichment for gene-ontology terms associated with T-cell activation, differentiation, and ...

Abstract	Analysis of the transcriptional profile of graft biopsies represents a promising strategy to study T cell-mediated-rejection (TCMR), also known as acute cellular rejection. However, bulk RNA sequencing of graft biopsies may not capture the focal nature of acute rejection. Herein, we used the whole exome GeoMX Digital Space Profiling platform to study five tubular and three glomerular regions of interest in the kidney graft biopsy from a patient with a chronic-active TCMR episode and in analogous areas from two different normal kidney control biopsies. All kidney sections were from paraffin blocks. Overall, inflammatory genes were significantly upregulated in the tubular areas of the TCMR biopsy and showed an enrichment for gene-ontology terms associated with T-cell activation, differentiation, and proliferation. Enrichment analysis of the 100 genes with the highest coefficient of variation across the TCMR tubular regions of interest revealed that these highly variable genes are involved in kidney development and injury and interestingly do not associate with the 2019 Banff classification pathology scores within the individual regions of interest. Spatial transcriptomics allowed us to unravel a previously unappreciated variability across different areas of the TCMR biopsy related to the graft response to the alloimmune attack, rather than to the immune cells. Thus, our approach has the potential to decipher clinically relevant, new pathogenic mechanisms, and therapeutic targets in acute cellular rejection and other kidney diseases with a focal nature.
MeSH term(s)	Allografts/pathology ; Biopsy ; Graft Rejection ; Humans ; Kidney/pathology ; Kidney Transplantation/adverse effects ; T-Lymphocytes
Language	English
Publishing date	2021-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2021.09.004
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Article ; Online: T-cell exhaustion correlates with improved outcomes in kidney transplant recipients.

Fribourg, Miguel / Anderson, Lisa / Fischman, Clara / Cantarelli, Chiara / Perin, Laura / La Manna, Gaetano / Rahman, Adeeb / Burrell, Bryna E / Heeger, Peter S / Cravedi, Paolo

Kidney international

2019 Volume 96, Issue 2, Page(s) 436–449

Abstract: Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell ... silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following ... of-flight mass cytometry (CyTOF) to define distinct subsets of circulating exhausted T cells and ...

Abstract	Continuous antigen stimulation during chronic infection or malignancy can promote functional T cell silencing, a phenomenon called T cell exhaustion. The prevalence and impact of T cell exhaustion following organ transplantation, another immune stimulus with persistently high antigen load, are unknown. Here, we characterized serially collected peripheral blood mononuclear cells from 26 kidney transplant recipients using time-of-flight mass cytometry (CyTOF) to define distinct subsets of circulating exhausted T cells and their relationship to induction therapy and allograft function. We observed an increase in specific subsets of CD4
MeSH term(s)	Adult ; Allografts/immunology ; Allografts/pathology ; Antilymphocyte Serum/administration & dosage ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD57 Antigens/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Female ; Fibrosis ; Graft Rejection/blood ; Graft Rejection/epidemiology ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Humans ; Immunosuppressive Agents/administration & dosage ; Kidney/immunology ; Kidney/pathology ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Postoperative Period ; Preoperative Period ; Programmed Cell Death 1 Receptor/metabolism ; Prospective Studies ; Risk Assessment/methods ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; Time Factors
Chemical Substances	Antilymphocyte Serum ; CD57 Antigens ; Immunosuppressive Agents ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-02-27
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2019.01.040
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Article ; Online: Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation.

Gandolfini, Ilaria / Crespo, Elena / Baweja, Mukta / Jarque, Marta / Donadei, Chiara / Luque, Sergio / Montero, Núria / Allesina, Anna / Perin, Laura / Maggiore, Umberto / Cravedi, Paolo / Bestard, Oriol

PloS one

2018 Volume 13, Issue 7, Page(s) e0200696

Abstract: ... of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells ... increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays ...

Abstract	Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6-65], 18 [8-37], and 26 [10-45] spots/3x105 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher Δ3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.
MeSH term(s)	Adult ; Aged ; Allografts/immunology ; Allografts/pathology ; B-Lymphocytes/immunology ; Biopsy ; Enzyme-Linked Immunospot Assay/methods ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Graft Rejection/diagnosis ; Graft Rejection/epidemiology ; Graft Rejection/immunology ; Graft Rejection/pathology ; Humans ; Immunologic Memory/immunology ; Interferon-gamma/analysis ; Interferon-gamma/immunology ; Interleukin-15/analysis ; Interleukin-15/immunology ; Isoantibodies/immunology ; Kidney/immunology ; Kidney/pathology ; Kidney/physiopathology ; Kidney Transplantation/adverse effects ; Male ; Middle Aged ; Monitoring, Immunologic/methods ; Postoperative Period ; Preoperative Period ; Prognosis ; Retrospective Studies ; T-Lymphocytes/immunology ; Tissue Donors
Chemical Substances	IL15 protein, human ; Interleukin-15 ; Isoantibodies ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2018-07-30
Publishing country	United States
Document type	Evaluation Studies ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0200696
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Article ; Online: Impact of preformed T-cell alloreactivity by means of donor-specific and panel of reactive T cells (PRT) ELISPOT in kidney transplantation.

Ilaria Gandolfini / Elena Crespo / Mukta Baweja / Marta Jarque / Chiara Donadei / Sergio Luque / Núria Montero / Anna Allesina / Laura Perin / Umberto Maggiore / Paolo Cravedi / Oriol Bestard

PLoS ONE, Vol 13, Iss 7, p e

2018 Volume 0200696

Abstract	Donor-specific (d-sp) interferon gamma enzyme-linked immunosorbent spot (d-sp ELISPOT) and Panel of reactive T-cell (PRT) ELISPOT assays have been developed to detect alloreactive memory T (Tmem) cells in order to estimate the risk of acute rejection after kidney transplantation. Adding IL15 to the PRT assay (PRT+IL15) may uncover the presence of pathogenic alloreactive CD28-Tmem. Face-to-face comparisons of these assays have not been done yet. We performed pre-transplant d-sp ELISPOT and PRT assays (±IL15, against six B-cell lines) in 168 consecutive kidney transplant recipients and evaluated the multivariable-adjusted associations with biopsy-proven acute rejection (BPAR), de novo donor-specific antibodies (DSA), and eGFR decline over a 48-month follow-up period. D-sp ELISPOT was positive in 81 (48%) subjects, while 71 (42%) and 81 (48%) subjects displayed positive PRT and PRT+IL15, respectively. Their median [interquartile range] numerical test result was 23 [6-65], 18 [8-37], and 26 [10-45] spots/3x105 PBMCs, respectively. The number of PRT spots were weakly correlated with those of d-sp ELISPOT, but highly correlated with PRT+IL15 (rho = 0.96, P<0.001). d-sp ELISPOT, but not PRT (±IL15) was independently associated with BPAR (adjusted Odds Ratio of BPAR associated with d-sp ELISPOT positivity: 4.20 [95%CI: 1.06 to 21.73; P = 0.041]). Unlike d-sp ELISPOT, median PRT and PRT+IL15 were independently associated with higher Δ3-48month eGFR decline post-transplantation (for both assays, about -3mL/min/1.73m2 per one standard deviation unit increase in the spot number). Pre-transplant T-cell immune-monitoring using d-sp ELISPOT and PRT assays identifies kidney transplant candidates at high risk of BPAR and worse kidney allograft progression.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Improved Natural Killer cell activity and retained anti-tumor CD8(+) T cell responses contribute to the induction of a pathological complete response in HER2-positive breast cancer patients undergoing neoadjuvant chemotherapy.

Muraro, E / Comaro, E / Talamini, R / Turchet, E / Miolo, G / Scalone, S / Militello, L / Lombardi, D / Spazzapan, S / Perin, T / Massarut, S / Crivellari, D / Dolcetti, Riccardo / Martorelli, D

Journal of translational medicine

2015 Volume 13, Page(s) 204

Abstract: ... The percentages of circulating immune cell subsets including T and B lymphocytes, Natural Killer (NK) cells ... regulatory T cells, T helper 17 lymphocytes, were quantified by multiparametric flow cytometry. NK cells ... CD8(+) T cell responses against six different tumor-associated antigens (TAA) were characterized ...

Abstract	Background: Locally advanced HER2-overexpressing breast cancer (BC) patients achieve a high rate of pathological complete responses (pCR) after neoadjuvant chemotherapy (NC). The apparently unaltered immune proficiency of these patients together with the immune-modulating activities of NC drugs suggest a potential contribution of host immunity in mediating clinical responses. We thus performed an extensive immunomonitoring in locally advanced BC patients undergoing NC to identify immunological correlates of pCR induction. Methods: The immune profile of 40 HER2-positive and 38 HER2-negative BC patients was characterized at diagnosis and throughout NC (Paclitaxel and Trastuzumab, or Docetaxel and Epirubicin, respectively). The percentages of circulating immune cell subsets including T and B lymphocytes, Natural Killer (NK) cells, regulatory T cells, T helper 17 lymphocytes, were quantified by multiparametric flow cytometry. NK cells functional activity was evaluated through the analysis of NF-kB nuclear translocation by Multispectral flow cytometry, and with the in vitro monitoring of Trastuzumab-mediated antibody-dependent cell cytotoxicity (ADCC). CD8(+) T cell responses against six different tumor-associated antigens (TAA) were characterized by IFN-γ ELISPOT and IFN-γ/IL-2 DualSpot assays. Results: After NC, HER2-positive patients showed a significant increase in the number of NK cells and regulatory T cells irrespective of the pathological response, whereas patients undergoing a pCR disclosed higher percentages of T helper 17 cells. Notably, a significant increase in the number of activated NK cells was observed only in HER2-positive patients achieving a pCR. Characterization of anti-tumor T cell responses highlighted sustained levels of CD8(+) T cells specific for survivin and mammaglobin-A throughout NC in patients undergoing a pCR in both arms. Moreover, HER2-positive patients achieving a pCR were characterized by a multi-epitopic and polyfunctional anti-tumor T cell response, markedly reduced in case of partial response. Conclusions: These results indicate that maintenance of functional T cell responses against selected antigens and improvement of NK cell proficiency during NC are probably critical requirements for pCR induction, especially in HER2-positive BC patients. Trail registration: Trial registration number: NCT02307227, registered on ClinicalTrials.gov ( http://www.clinicaltrials.gov , November 26, 2014).
MeSH term(s)	Adaptive Immunity/drug effects ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Female ; Humans ; Immunity, Innate/drug effects ; Immunophenotyping ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Middle Aged ; NF-kappa B/metabolism ; Neoadjuvant Therapy ; Paclitaxel/pharmacology ; Paclitaxel/therapeutic use ; Receptor, ErbB-2/metabolism ; Remission Induction ; Trastuzumab/pharmacology ; Trastuzumab/therapeutic use ; Treatment Outcome
Chemical Substances	NF-kappa B ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2015-06-27
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-015-0567-0
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Article ; Online: Human immunodeficiency virus-associated precursor T-lymphoblastic leukemia/lymphoblastic lymphoma: report of a case and review of the literature.

Lorenzon, Debora / Perin, Tiziana / Bulian, Pietro / De Re, Valli / Caggiari, Laura / Michieli, Mariagrazia / Manuele, Rosa / Spina, Michele / Gattei, Valter / Fasan, Marco / Tirelli, Umberto / Canzonieri, Vincenzo

Human pathology

2009 Volume 40, Issue 7, Page(s) 1045–1049

Abstract: We describe a case of human immunodeficiency virus-associated T-lymphoblastic leukemia ... by Ki-67/MIB-1 staining. Flow cytometry of the marrow aspirate revealed an intermediate/cortical T ... and CD8, with partial coexpression of dimCD4. Analysis of T-cell receptor gamma ...

Abstract	We describe a case of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma in a 43-year-old Italian man with a history of human immunodeficiency virus infection lasting 9 years. Immunoperoxidase stains showed that neoplastic cells were positive for CD3, TdT, CD45, CD10, CD1a, CD2, CD7, CD5, and CD43 (focal). The proliferation rate was approximately 70%, assessed by Ki-67/MIB-1 staining. Flow cytometry of the marrow aspirate revealed an intermediate/cortical T-lymphoblastic phenotype: negative for surface CD3 and positive for cytoplasmic CD3, CD1a, TdT, CD2, CD7, CD5, and CD8, with partial coexpression of dimCD4. Analysis of T-cell receptor gamma polymerase chain reaction products showed clonality. T-lymphoblastic leukemia/lymphoblastic lymphoma is a very rare occurrence in the clinical setting of human immunodeficiency virus infection. It is not listed in the World Health Organization classification of lymphomas associated with human immunodeficiency virus infection. Only 4 cases of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma are reported in the current medical literature.
MeSH term(s)	Adult ; Base Sequence ; Fatal Outcome ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; HIV Infections/pathology ; Humans ; Leukemia, Lymphoid/pathology ; Leukemia, Lymphoid/virology ; Male ; Molecular Sequence Data ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology
Language	English
Publishing date	2009-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2008.12.021
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Zs.A 722: Show issues

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Article ; Online: Human mesenchymal stem cell-derived microvesicles modulate T cell response to islet antigen glutamic acid decarboxylase in patients with type 1 diabetes.

Favaro, Enrica / Carpanetto, Andrea / Lamorte, Sara / Fusco, Alberto / Caorsi, Cristiana / Deregibus, Maria C / Bruno, Stefania / Amoroso, Antonio / Giovarelli, Mirella / Porta, Massimo / Perin, Paolo Cavallo / Tetta, Ciro / Camussi, Giovanni / Zanone, Maria M

Diabetologia

2014 Volume 57, Issue 8, Page(s) 1664–1673

Abstract: ... an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes ... and prostaglandin E2 (PGE2) were measured in the supernatant fraction, and T helper 17 (Th17) and ... regulatory T cell analysis was performed.: Results: MVs were internalised by PBMCs, as assessed ...

Abstract	Aims/hypothesis: Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes. Methods: MVs were purified from heterologous human MSCs by differential centrifugation. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with type 1 diabetes at disease onset, and responses to GAD65 stimulation were assessed by IFN-γ enzyme-linked immunosorbent spot analysis. Levels of cytokines and prostaglandin E2 (PGE2) were measured in the supernatant fraction, and T helper 17 (Th17) and regulatory T cell analysis was performed. Results: MVs were internalised by PBMCs, as assessed by confocal microscopy and flow cytometry analyses. MVs significantly decreased IFN-γ spots and levels in GAD65-stimulated PBMCs, and significantly increased transforming growth factor-β (TGF-β), IL-10, IL-6 and PGE2 levels. Furthermore, MVs decreased the number of Th17 cells and the levels of IL-17, and increased FoxP3(+) regulatory T cells in GAD65-stimulated PBMCs. Conclusions/interpretation: These results provide evidence that MSC-derived MVs can inhibit in vitro a proinflammatory response to an islet antigenic stimulus in type 1 diabetes. The action of MVs involves PGE2 and TGF-β signalling pathways and IL-10 secretion, suggesting a switch to an anti-inflammatory response of T cells.
MeSH term(s)	Adult ; Cytokines/metabolism ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/metabolism ; Dinoprostone/metabolism ; Female ; Glutamate Decarboxylase/immunology ; Humans ; Male ; Mesenchymal Stem Cells/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Young Adult
Chemical Substances	Cytokines ; Glutamate Decarboxylase (EC 4.1.1.15) ; Dinoprostone (K7Q1JQR04M)
Language	English
Publishing date	2014-05-17
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-014-3262-4
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Article ; Online: Assessment of photosynthetic activity in dense microalgae cultures using oxygen production.

Vera-Vives, Antoni Mateu / Michelberger, Tim / Morosinotto, Tomas / Perin, Giorgio

Plant physiology and biochemistry : PPB

2024 Volume 208, Page(s) 108510

Abstract: Microalgae are photosynthetic microorganisms playing a pivotal role in primary production in aquatic ecosystems, sustaining the entry of carbon in the biosphere. Microalgae have also been recognized as sustainable source of biomass to complement crops. ... ...

Abstract	Microalgae are photosynthetic microorganisms playing a pivotal role in primary production in aquatic ecosystems, sustaining the entry of carbon in the biosphere. Microalgae have also been recognized as sustainable source of biomass to complement crops. For this objective they are cultivated in photobioreactors or ponds at high cell density to maximize biomass productivity and lower the cost of downstream processes. Photosynthesis depends on light availability, that is often not constant over time. In nature, sunlight fluctuates over diurnal cycles and weather conditions. In high-density microalgae cultures of photobioreactors outdoors, on top of natural variations, microalgae are subjected to further complexity in light exposure. Because of the high-density cells experience self-shading effects that heavily limit light availability in most of the mass culture volume. This limitation strongly affects biomass productivity of industrial microalgae cultivation plants with important implications on economic feasibility. Understanding how photosynthesis responds to cell density is informative to assess functionality in the inhomogeneous light environment of industrial photobioreactors. In this work we exploited a high-sensitivity Clark electrode to measure microalgae photosynthesis and compare cultures with different densities, using Nannochloropsis as model organism. We observed that cell density has a substantial impact on photosynthetic activity, and demonstrated the reduction of the cell's light-absorption capacity by genetic modification is a valuable strategy to increase photosynthetic functionality on a chlorophyll-basis of dense microalgae cultures.
MeSH term(s)	Microalgae ; Ecosystem ; Oxygen/metabolism ; Photosynthesis ; Photobioreactors ; Biomass
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2024-03-07
Publishing country	France
Document type	Journal Article
ZDB-ID	742978-2
ISSN	1873-2690 ; 0981-9428
ISSN (online)	1873-2690
ISSN	0981-9428
DOI	10.1016/j.plaphy.2024.108510
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Article ; Online: ICARUS: flexible protein structural alignment based on Protein Units.

Cretin, Gabriel / Périn, Charlotte / Zimmermann, Nicolas / Galochkina, Tatiana / Gelly, Jean-Christophe

Bioinformatics (Oxford, England)

2023 Volume 39, Issue 8

Abstract: Motivation: Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational ... ...

Abstract	Motivation: Alignment of protein structures is a major problem in structural biology. The first approach commonly used is to consider proteins as rigid bodies. However, alignment of protein structures can be very complex due to conformational variability, or complex evolutionary relationships between proteins such as insertions, circular permutations or repetitions. In such cases, introducing flexibility becomes useful for two reasons: (i) it can help compare two protein chains which adopted two different conformational states, such as due to proteins/ligands interaction or post-translational modifications, and (ii) it aids in the identification of conserved regions in proteins that may have distant evolutionary relationships. Results: We propose ICARUS, a new approach for flexible structural alignment based on identification of Protein Units, evolutionarily preserved structural descriptors of intermediate size, between secondary structures and domains. ICARUS significantly outperforms reference methods on a dataset of very difficult structural alignments. Availability and implementation: Code is freely available online at https://github.com/DSIMB/ICARUS.
MeSH term(s)	Algorithms ; Sequence Alignment ; Proteins/chemistry ; Protein Structure, Secondary ; Biological Evolution ; Software
Chemical Substances	Proteins
Language	English
Publishing date	2023-07-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btad459
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