LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 31

Search options

  1. Article ; Online: Transcriptomics and Spatial Proteomics for Discovery and Validation of Missing Proteins in the Human Ovary.

    Méar, Loren / Hao, Xia / Hikmet, Feria / Damdimopoulou, Pauliina / Rodriguez-Wallberg, Kenny A / Lindskog, Cecilia

    Journal of proteome research

    2023  Volume 23, Issue 1, Page(s) 238–248

    Abstract: Efforts to understand the complexities of human biology encompass multidimensional aspects, with proteins emerging as crucial components. However, studying the human ovary introduces unique challenges due to its complex dynamics and changes over a ... ...

    Abstract Efforts to understand the complexities of human biology encompass multidimensional aspects, with proteins emerging as crucial components. However, studying the human ovary introduces unique challenges due to its complex dynamics and changes over a lifetime, varied cellular composition, and limited sample access. Here, four new RNA-seq samples of ovarian cortex spanning ages of 7 to 32 were sequenced and added to the existing data in the Human Protein Atlas (HPA) database www.proteinatlas.org, opening the doors to unique possibilities for exploration of oocyte-specific proteins. Based on transcriptomics analysis of the four new tissue samples representing both prepubertal girls and women of fertile age, we selected 20 protein candidates that lacked previous evidence at the protein level, so-called "missing proteins" (MPs). The proteins were validated using high-resolution antibody-based profiling and single-cell transcriptomics. Fourteen proteins exhibited consistent single-cell expression patterns in oocytes and granulosa cells, confirming their presence in the ovary and suggesting that these proteins play important roles in ovarian function, thus proposing that these 14 proteins should no longer be classified as MPs. This research significantly advances the understanding of MPs, unearthing fresh avenues for prospective exploration. By integrating innovative methodologies and leveraging the wealth of data in the HPA database, these insights contribute to refining our understanding of protein roles within the human ovary and opening the doors for further investigations into missing proteins and human reproduction.
    MeSH term(s) Humans ; Female ; Ovary ; Proteomics ; Prospective Studies ; Oocytes ; Proteins/metabolism ; Gene Expression Profiling
    Chemical Substances Proteins
    Language English
    Publishing date 2023-12-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.3c00545
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: DeepHistoClass: A Novel Strategy for Confident Classification of Immunohistochemistry Images Using Deep Learning.

    Ghoshal, Biraja / Hikmet, Feria / Pineau, Charles / Tucker, Allan / Lindskog, Cecilia

    Molecular & cellular proteomics : MCP

    2021  Volume 20, Page(s) 100140

    Abstract: A multitude of efforts worldwide aim to create a single-cell reference map of the human body, for fundamental understanding of human health, molecular medicine, and targeted treatment. Antibody-based proteomics using immunohistochemistry (IHC) has proven ...

    Abstract A multitude of efforts worldwide aim to create a single-cell reference map of the human body, for fundamental understanding of human health, molecular medicine, and targeted treatment. Antibody-based proteomics using immunohistochemistry (IHC) has proven to be an excellent technology for integration with large-scale single-cell transcriptomics datasets. The golden standard for evaluation of IHC staining patterns is manual annotation, which is expensive and may lead to subjective errors. Artificial intelligence holds much promise for efficient and accurate pattern recognition, but confidence in prediction needs to be addressed. Here, the aim was to present a reliable and comprehensive framework for automated annotation of IHC images. We developed a multilabel classification of 7848 complex IHC images of human testis corresponding to 2794 unique proteins, generated as part of the Human Protein Atlas (HPA) project. Manual annotation data for eight different cell types was generated as a basis for training and testing a proposed Hybrid Bayesian Neural Network. By combining the deep learning model with a novel uncertainty metric, DeepHistoClass (DHC) Confidence Score, the average diagnostic performance improved from 86.9% to 96.3%. This metric not only reveals which images are reliably classified by the model, but can also be utilized for identification of manual annotation errors. The proposed streamlined workflow can be developed further for other tissue types in health and disease and has important implications for digital pathology initiatives or large-scale protein mapping efforts such as the HPA project.
    MeSH term(s) Bayes Theorem ; Deep Learning ; Humans ; Image Processing, Computer-Assisted/methods ; Immunohistochemistry/classification ; Male ; Proteins/metabolism ; Testis/metabolism ; Workflow
    Chemical Substances Proteins
    Language English
    Publishing date 2021-08-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2075924-1
    ISSN 1535-9484 ; 1535-9476
    ISSN (online) 1535-9484
    ISSN 1535-9476
    DOI 10.1016/j.mcpro.2021.100140
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: The protein expression profile of ACE2 in human tissues

    Feria Hikmet / Loren Méar / Mathias Uhlén / Cecilia Lindskog

    Abstract: ABSTRACTThe international spread of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on both healthcare and society. A multitude of research efforts worldwide aim at characterizing the cellular factors involved in viral ... ...

    Abstract ABSTRACTThe international spread of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on both healthcare and society. A multitude of research efforts worldwide aim at characterizing the cellular factors involved in viral transmission in order to reveal therapeutic targets. For a full understanding of the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2), and its expression has been reported in various human organs, in some cases with inconsistent or contradictory results. Here, we aim to verify a reliable expression profile of ACE2 in all major human tissues and cell types. Based on stringently validated immunohistochemical analysis and high-throughput mRNA sequencing from several datasets, we found that ACE2 expression is mainly localized to microvilli of the intestinal tract and renal proximal tubules, gallbladder epithelium, testicular Sertoli cells and Leydig cells, glandular cells of seminal vesicle and cardiomyocytes. The expression in several other previously reported locations, including alveolar type II (AT2) cells, could not be confirmed. Furthermore, ACE2 expression was absent in the AT2 lung carcinoma cell line A549, often used as a model for viral replication studies. Our analysis suggests that the expression of ACE2 in the human respiratory system appears to be limited, and the expression of the receptor in lung or respiratory epithelia on the protein level is yet to be confirmed. This raises questions regarding the role of ACE2 for infection of human lungs and highlights the need to further explore the route of transmission during SARS-CoV-2 infection.
    Keywords covid19
    Publisher biorxiv
    Document type Article ; Online
    DOI 10.1101/2020.03.31.016048
    Database COVID19

    Kategorien

  4. Article ; Online: Expression of cancer-testis antigens in the immune microenvironment of non-small cell lung cancer.

    Hikmet, Feria / Rassy, Marc / Backman, Max / Méar, Loren / Mattsson, Johanna Sofia Margareta / Djureinovic, Dijana / Botling, Johan / Brunnström, Hans / Micke, Patrick / Lindskog, Cecilia

    Molecular oncology

    2023  Volume 17, Issue 12, Page(s) 2603–2617

    Abstract: The antigenic repertoire of tumors is critical for successful anti-cancer immune response and the efficacy of immunotherapy. Cancer-testis antigens (CTAs) are targets of humoral and cellular immune reactions. We aimed to characterize CTA expression in ... ...

    Abstract The antigenic repertoire of tumors is critical for successful anti-cancer immune response and the efficacy of immunotherapy. Cancer-testis antigens (CTAs) are targets of humoral and cellular immune reactions. We aimed to characterize CTA expression in non-small cell lung cancer (NSCLC) in the context of the immune microenvironment. Of 90 CTAs validated by RNA sequencing, eight CTAs (DPEP3, EZHIP, MAGEA4, MAGEB2, MAGEC2, PAGE1, PRAME, and TKTL1) were selected for immunohistochemical profiling in cancer tissues from 328 NSCLC patients. CTA expression was compared with immune cell densities in the tumor environment and with genomic, transcriptomic, and clinical data. Most NSCLC cases (79%) expressed at least one of the analyzed CTAs, and CTA protein expression correlated generally with RNA expression. CTA profiles were associated with immune profiles: high MAGEA4 expression was related to M2 macrophages (CD163) and regulatory T cells (FOXP3), low MAGEA4 was associated with T cells (CD3), and high EZHIP was associated with plasma cell infiltration (adj. P-value < 0.05). None of the CTAs correlated with clinical outcomes. The current study provides a comprehensive evaluation of CTAs and suggests that their association with immune cells may indicate in situ immunogenic effects. The findings support the rationale to harness CTAs as targets for immunotherapy.
    MeSH term(s) Male ; Humans ; Carcinoma, Non-Small-Cell Lung/metabolism ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Lung Neoplasms/metabolism ; Testis/metabolism ; Testis/pathology ; Neoplasm Proteins/metabolism ; Tumor Microenvironment ; Transketolase/metabolism
    Chemical Substances Antigens, Neoplasm ; Neoplasm Proteins ; PRAME protein, human ; TKTL1 protein, human (EC 2.2.1.1) ; Transketolase (EC 2.2.1.1)
    Language English
    Publishing date 2023-06-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13474
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: The protein expression profile of ACE2 in human tissues

    Hikmet, Feria / Méar, Loren / Uhlén, Mathias / Lindskog, Cecilia

    bioRxiv

    Abstract: The international spread of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on both healthcare and society. A multitude of research efforts worldwide aim at characterizing the cellular factors involved in viral transmission ...

    Abstract The international spread of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on both healthcare and society. A multitude of research efforts worldwide aim at characterizing the cellular factors involved in viral transmission in order to reveal therapeutic targets. For a full understanding of the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2), and its expression has been reported in various human organs, in some cases with inconsistent or contradictory results. Here, we aim to verify a reliable expression profile of ACE2 in all major human tissues and cell types. Based on stringently validated immunohistochemical analysis and high-throughput mRNA sequencing from several datasets, we found that ACE2 expression is mainly localized to microvilli of the intestinal tract and renal proximal tubules, gallbladder epithelium, testicular Sertoli cells and Leydig cells, glandular cells of seminal vesicle and cardiomyocytes. The expression in several other previously reported locations, including alveolar type II (AT2) cells, could not be confirmed. Furthermore, ACE2 expression was absent in the AT2 lung carcinoma cell line A549, often used as a model for viral replication studies. Our analysis suggests that the expression of ACE2 in the human respiratory system appears to be limited, and the expression of the receptor in lung or respiratory epithelia on the protein level is yet to be confirmed. This raises questions regarding the role of ACE2 for infection of human lungs and highlights the need to further explore the route of transmission during SARS-CoV-2 infection.
    Keywords covid19
    Language English
    Publishing date 2020-04-03
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.03.31.016048
    Database COVID19

    Kategorien

  6. Article ; Online: The protein expression profile of ACE2 in human tissues.

    Hikmet, Feria / Méar, Loren / Edvinsson, Åsa / Micke, Patrick / Uhlén, Mathias / Lindskog, Cecilia

    Molecular systems biology

    2020  Volume 16, Issue 7, Page(s) e9610

    Abstract: The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein ...

    Abstract The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitute an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.
    MeSH term(s) Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; Blood Vessels/metabolism ; Conjunctiva/metabolism ; Enterocytes/metabolism ; Female ; Gallbladder/metabolism ; Host Microbial Interactions ; Humans ; Immunohistochemistry ; Kidney Tubules, Proximal/metabolism ; Male ; Mass Spectrometry ; Myocytes, Cardiac/metabolism ; Organ Specificity ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Placenta/metabolism ; Pregnancy ; RNA-Seq ; Respiratory System/metabolism ; SARS-CoV-2 ; Single-Cell Analysis ; Testis/metabolism
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-10-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193510-5
    ISSN 1744-4292 ; 1744-4292
    ISSN (online) 1744-4292
    ISSN 1744-4292
    DOI 10.15252/msb.20209610
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: The protein expression profile of ACE2 in human tissues

    Feria Hikmet / Loren Méar / Åsa Edvinsson / Patrick Micke / Mathias Uhlén / Cecilia Lindskog

    Molecular Systems Biology, Vol 16, Iss 7, Pp n/a-n/a (2020)

    2020  

    Abstract: Abstract The novel SARS‐coronavirus 2 (SARS‐CoV‐2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS‐CoV‐2 infection, the cell type‐specific expression of the host cell surface receptor is necessary. The ... ...

    Abstract Abstract The novel SARS‐coronavirus 2 (SARS‐CoV‐2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS‐CoV‐2 infection, the cell type‐specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitute an important resource for further studies on SARS‐CoV‐2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.
    Keywords ACE2 ; immunohistochemistry ; respiratory system ; SARS‐CoV-2 ; transcriptomics ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article ; Online: Combined RNA/tissue profiling identifies novel Cancer/testis genes.

    Jamin, Soazik P / Hikmet, Feria / Mathieu, Romain / Jégou, Bernard / Lindskog, Cecilia / Chalmel, Frédéric / Primig, Michael

    Molecular oncology

    2021  Volume 15, Issue 11, Page(s) 3003–3023

    Abstract: Cancer/Testis (CT) genes are induced in germ cells, repressed in somatic cells, and derepressed in somatic tumors, where these genes can contribute to cancer progression. CT gene identification requires data obtained using standardized protocols and ... ...

    Abstract Cancer/Testis (CT) genes are induced in germ cells, repressed in somatic cells, and derepressed in somatic tumors, where these genes can contribute to cancer progression. CT gene identification requires data obtained using standardized protocols and technologies. This is a challenge because data for germ cells, gonads, normal somatic tissues, and a wide range of cancer samples stem from multiple sources and were generated over substantial periods of time. We carried out a GeneChip-based RNA profiling analysis using our own data for testis and enriched germ cells, data for somatic cancers from the Expression Project for Oncology, and data for normal somatic tissues from the Gene Omnibus Repository. We identified 478 candidate loci that include known CT genes, numerous genes associated with oncogenic processes, and novel candidates that are not referenced in the Cancer/Testis Database (www.cta.lncc.br). We complemented RNA expression data at the protein level for SPESP1, GALNTL5, PDCL2, and C11orf42 using cancer tissue microarrays covering malignant tumors of breast, uterus, thyroid, and kidney, as well as published RNA profiling and immunohistochemical data provided by the Human Protein Atlas (www.proteinatlas.org). We report that combined RNA/tissue profiling identifies novel CT genes that may be of clinical interest as therapeutical targets or biomarkers. Our findings also highlight the challenges of detecting truly germ cell-specific mRNAs and the proteins they encode in highly heterogenous testicular, somatic, and tumor tissues.
    MeSH term(s) Gene Expression Profiling ; Humans ; Male ; N-Acetylgalactosaminyltransferases ; Oligonucleotide Array Sequence Analysis ; RNA ; Testicular Neoplasms
    Chemical Substances RNA (63231-63-0) ; GALNTL5 protein, human (EC 2.4.1.-) ; N-Acetylgalactosaminyltransferases (EC 2.4.1.-)
    Language English
    Publishing date 2021-06-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.12900
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Generation of three human induced pluripotent stem cell (iPSC) lines from three patients with Dravet syndrome carrying distinct SCN1A gene mutations

    Jens Schuster / Ambrin Fatima / Maria Sobol / Feria Hikmet Norradin / Loora Laan / Niklas Dahl

    Stem Cell Research, Vol 39, Iss , Pp - (2019)

    2019  

    Abstract: Dravet syndrome (DS) is a childhood epilepsy syndrome caused by heterozygous mutations in the SCN1A gene encoding voltage-gated sodium channel Nav1.1. We generated iPSCs from fibroblasts of three DS patients carrying distinct SCN1A mutations (c.5502- ... ...

    Abstract Dravet syndrome (DS) is a childhood epilepsy syndrome caused by heterozygous mutations in the SCN1A gene encoding voltage-gated sodium channel Nav1.1. We generated iPSCs from fibroblasts of three DS patients carrying distinct SCN1A mutations (c.5502-5509dupGCTTGAAC, c.2965G>C and c.651C>G). The iPSC lines were genetically stable and each line retained the SCN1A gene mutation of the donor fibroblasts. Characterization of the iPSC lines confirmed expression of pluripotency markers, absence of exogenous vector expression and trilineage differentiation potential. These iPSC lines offer a useful resource to investigate the molecular mechanisms underlying Nav1.1 haploinsufficiency and for drug development to improve treatment of DS patients.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Article ; Online: The protein expression profile of ACE2 in human tissues

    Hikmet, Feria / Mear, Loren / Edvinsson, Asa / Micke, Patrick / Uhlen, Mathias / Lindskog, Cecilia

    bioRxiv

    Abstract: The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein ...

    Abstract The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across >150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitutes an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.
    Keywords covid19
    Publisher BioRxiv; WHO
    Document type Article ; Online
    Note WHO #Covidence: #016048
    DOI 10.1101/2020.03.31.016048
    Database COVID19

    Kategorien

To top