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  1. Article: Machine Learning of Raman Spectroscopy Data for Classifying Cancers: A Review of the Recent Literature.

    Blake, Nathan / Gaifulina, Riana / Griffin, Lewis D / Bell, Ian M / Thomas, Geraint M H

    Diagnostics (Basel, Switzerland)

    2022  Volume 12, Issue 6

    Abstract: Raman Spectroscopy has long been anticipated to augment clinical decision making, such as classifying oncological samples. Unfortunately, the complexity of Raman data has thus far inhibited their routine use in clinical settings. Traditional machine ... ...

    Abstract Raman Spectroscopy has long been anticipated to augment clinical decision making, such as classifying oncological samples. Unfortunately, the complexity of Raman data has thus far inhibited their routine use in clinical settings. Traditional machine learning models have been used to help exploit this information, but recent advances in deep learning have the potential to improve the field. However, there are a number of potential pitfalls with both traditional and deep learning models. We conduct a literature review to ascertain the recent machine learning methods used to classify cancers using Raman spectral data. We find that while deep learning models are popular, and ostensibly outperform traditional learning models, there are many methodological considerations which may be leading to an over-estimation of performance; primarily, small sample sizes which compound sub-optimal choices regarding sampling and validation strategies. Amongst several recommendations is a call to collate large benchmark Raman datasets, similar to those that have helped transform digital pathology, which researchers can use to develop and refine deep learning models.
    Language English
    Publishing date 2022-06-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics12061491
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Deep Learning Applied to Raman Spectroscopy for the Detection of Microsatellite Instability/MMR Deficient Colorectal Cancer.

    Blake, Nathan / Gaifulina, Riana / Griffin, Lewis D / Bell, Ian M / Rodriguez-Justo, Manuel / Thomas, Geraint M H

    Cancers

    2023  Volume 15, Issue 6

    Abstract: Defective DNA mismatch repair is one pathogenic pathway to colorectal cancer. It is characterised by microsatellite instability which provides a molecular biomarker for its detection. Clinical guidelines for universal testing of this biomarker are not ... ...

    Abstract Defective DNA mismatch repair is one pathogenic pathway to colorectal cancer. It is characterised by microsatellite instability which provides a molecular biomarker for its detection. Clinical guidelines for universal testing of this biomarker are not met due to resource limitations; thus, there is interest in developing novel methods for its detection. Raman spectroscopy (RS) is an analytical tool able to interrogate the molecular vibrations of a sample to provide a unique biochemical fingerprint. The resulting datasets are complex and high-dimensional, making them an ideal candidate for deep learning, though this may be limited by small sample sizes. This study investigates the potential of using RS to distinguish between normal, microsatellite stable (MSS) and microsatellite unstable (MSI-H) adenocarcinoma in human colorectal samples and whether deep learning provides any benefit to this end over traditional machine learning models. A 1D convolutional neural network (CNN) was developed to discriminate between healthy, MSI-H and MSS in human tissue and compared to a principal component analysis-linear discriminant analysis (PCA-LDA) and a support vector machine (SVM) model. A nested cross-validation strategy was used to train 30 samples, 10 from each group, with a total of 1490 Raman spectra. The CNN achieved a sensitivity and specificity of 83% and 45% compared to PCA-LDA, which achieved a sensitivity and specificity of 82% and 51%, respectively. These are competitive with existing guidelines, despite the low sample size, speaking to the molecular discriminative power of RS combined with deep learning. A number of biochemical antecedents responsible for this discrimination are also explored, with Raman peaks associated with nucleic acids and collagen being implicated.
    Language English
    Publishing date 2023-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15061720
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rapid and complete paraffin removal from human tissue sections delivers enhanced Raman spectroscopic and histopathological analysis.

    Gaifulina, Riana / Caruana, Daren J / Oukrif, Dahmane / Guppy, Naomi J / Culley, Siân / Brown, Robert / Bell, Ian / Rodriguez-Justo, Manuel / Lau, Katherine / Thomas, Geraint M H

    The Analyst

    2019  Volume 145, Issue 4, Page(s) 1499–1510

    Abstract: Incomplete removal of paraffin and organic contaminants from tissues processed for diagnostic histology has been a profound barrier to the introduction of Raman spectroscopic techniques into clinical practice. We report a route to rapid and complete ... ...

    Abstract Incomplete removal of paraffin and organic contaminants from tissues processed for diagnostic histology has been a profound barrier to the introduction of Raman spectroscopic techniques into clinical practice. We report a route to rapid and complete paraffin removal from a range of formalin-fixed paraffin embedded tissues using super mirror stainless steel slides. The method is equally effective on a range of human and animal tissues, performs equally well with archived and new samples and is compatible with standard pathology lab procedures. We describe a general enhancement of the Raman scatter and enhanced staining with antibodies used in immunohistochemistry for clinical diagnosis. We conclude that these novel slide substrates have the power to improve diagnosis through anatomical pathology by facilitating the simultaneous combination of improved, more sensitive immunohistochemical staining and simplified, more reliable Raman spectroscopic imaging, analysis and signal processing.
    MeSH term(s) Humans ; Paraffin/isolation & purification ; Paraffin Embedding ; Pathology/methods ; Spectrum Analysis, Raman/methods ; Time Factors
    Chemical Substances Paraffin (8002-74-2)
    Language English
    Publishing date 2019-12-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 210747-8
    ISSN 1364-5528 ; 0003-2654
    ISSN (online) 1364-5528
    ISSN 0003-2654
    DOI 10.1039/c9an01030k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Label-free Raman spectroscopic imaging to extract morphological and chemical information from a formalin-fixed, paraffin-embedded rat colon tissue section.

    Gaifulina, Riana / Maher, Andrew Thomas / Kendall, Catherine / Nelson, James / Rodriguez-Justo, Manuel / Lau, Katherine / Thomas, Geraint Mark

    International journal of experimental pathology

    2016  Volume 97, Issue 4, Page(s) 337–350

    Abstract: Animal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical features and to facilitate long-term storage, a majority of tissue ... ...

    Abstract Animal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical features and to facilitate long-term storage, a majority of tissue samples are denatured by the chemical treatments required for fixation, paraffin embedding and subsequent deparaffinization. These aggressive chemical processes are thought to modify the biochemical composition of the sample and potentially compromise reliable spectroscopic examination useful for the diagnosis or biomarking. As a result, spectroscopy is often conducted on fresh/frozen samples. In this study, we provide an extensive characterization of the biochemical signals remaining in processed samples (formalin fixation and paraffin embedding, FFPE) and especially those originating from the anatomical layers of a healthy rat colon. The application of chemometric analytical methods (unsupervised and supervised) was shown to eliminate the need for tissue staining and easily revealed microscopic features consistent with goblet cells and the dense populations of cells within the mucosa, principally via strong nucleic acid signals. We were also able to identify the collagenous submucosa- and serosa- as well as the muscle-associated signals from the muscular regions and blood vessels. Applying linear regression analysis to the data, we were able to corroborate this initial assignment of cell and tissue types by confirming the biological origin of each layer by reference to a subset of authentic biomolecular standards. Our results demonstrate the potential of using label-free Raman microspectroscopy to obtain superior imaging contrast in FFPE sections when compared directly to conventional haematoxylin and eosin (H&E) staining.
    MeSH term(s) Animals ; Colon/anatomy & histology ; Colon/chemistry ; Fixatives ; Formaldehyde ; Intestinal Mucosa/anatomy & histology ; Intestinal Mucosa/chemistry ; Paraffin Embedding/methods ; Principal Component Analysis ; Rats, Wistar ; Spectrum Analysis, Raman/methods ; Tissue Fixation/methods
    Chemical Substances Fixatives ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2016
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1016006-1
    ISSN 1365-2613 ; 0958-4625 ; 0007-1021 ; 0959-9673
    ISSN (online) 1365-2613
    ISSN 0958-4625 ; 0007-1021 ; 0959-9673
    DOI 10.1111/iep.12194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure.

    Meran, Laween / Massie, Isobel / Campinoti, Sara / Weston, Anne E / Gaifulina, Riana / Tullie, Lucinda / Faull, Peter / Orford, Michael / Kucharska, Anna / Baulies, Anna / Novellasdemunt, Laura / Angelis, Nikolaos / Hirst, Elizabeth / König, Julia / Tedeschi, Alfonso Maria / Pellegata, Alessandro Filippo / Eli, Susanna / Snijders, Ambrosius P / Collinson, Lucy /
    Thapar, Nikhil / Thomas, Geraint M H / Eaton, Simon / Bonfanti, Paola / De Coppi, Paolo / Li, Vivian S W

    Nature medicine

    2020  Volume 26, Issue 10, Page(s) 1593–1601

    Abstract: Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for ... ...

    Abstract Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children
    MeSH term(s) Animals ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Child ; Enterocytes/pathology ; Enterocytes/physiology ; Enterocytes/transplantation ; Extracellular Matrix/pathology ; Female ; HEK293 Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Intestinal Diseases/congenital ; Intestinal Diseases/pathology ; Intestinal Diseases/therapy ; Intestinal Mucosa/cytology ; Intestinal Mucosa/pathology ; Intestinal Mucosa/transplantation ; Jejunum/cytology ; Jejunum/pathology ; Jejunum/transplantation ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Organoids/pathology ; Precision Medicine/methods ; Primary Cell Culture/methods ; Proof of Concept Study ; Swine ; Tissue Engineering/methods ; Tissue Scaffolds
    Language English
    Publishing date 2020-09-07
    Publishing country United States
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-020-1024-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Developing Raman spectroscopy as a diagnostic tool for label-free antigen detection.

    Lewis, Aaran T / Gaifulina, Riana / Guppy, Naomi J / Isabelle, Martin / Dorney, Jennifer / Lloyd, Gavin R / Rodriguez-Justo, Manuel / Kendall, Catherine / Stone, Nicholas / Thomas, Geraint M

    Journal of biophotonics

    2017  Volume 11, Issue 2

    Abstract: For several decades, a multitude of studies have documented the ability of Raman spectroscopy (RS) to differentiate between tissue types and identify pathological changes to tissues in a range of diseases. Furthermore, spectroscopists have illustrated ... ...

    Abstract For several decades, a multitude of studies have documented the ability of Raman spectroscopy (RS) to differentiate between tissue types and identify pathological changes to tissues in a range of diseases. Furthermore, spectroscopists have illustrated that the technique is capable of detecting disease-specific alterations to tissue before morphological changes become apparent to the pathologist. This study draws comparisons between the information that is obtainable using RS alongside immunohistochemistry (IHC), since histological examination is the current GOLD standard for diagnosing a wide range of diseases. Here, Raman spectral maps were generated using formalin-fixed, paraffin-embedded colonic tissue sections from healthy patients and spectral signatures from principal components analysis (PCA) were compared with several IHC markers to confirm the validity of their localizations. PCA loadings identified a number of signatures that could be assigned to muscle, DNA and mucin glycoproteins and their distributions were confirmed with antibodies raised against anti-Desmin, anti-Ki67 and anti-MUC2, respectively. The comparison confirms that there is excellent correlation between RS and the IHC markers used, demonstrating that the technique is capable of detecting compositional changes in tissue in a label-free manner, eliminating the need for antibodies.
    MeSH term(s) Antigens/analysis ; Colon/cytology ; Formaldehyde ; Humans ; Paraffin Embedding ; Spectrum Analysis, Raman/methods ; Tissue Fixation
    Chemical Substances Antigens ; Formaldehyde (1HG84L3525)
    Language English
    Publishing date 2017-08-07
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2390063-5
    ISSN 1864-0648 ; 1864-063X
    ISSN (online) 1864-0648
    ISSN 1864-063X
    DOI 10.1002/jbio.201700028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mirrored stainless steel substrate provides improved signal for Raman spectroscopy of tissue and cells.

    Lewis, Aaran T / Gaifulina, Riana / Isabelle, Martin / Dorney, Jennifer / Woods, Mae L / Lloyd, Gavin R / Lau, Katherine / Rodriguez-Justo, Manuel / Kendall, Catherine / Stone, Nicholas / Thomas, Geraint M

    Journal of Raman spectroscopy : JRS

    2016  Volume 48, Issue 1, Page(s) 119–125

    Abstract: Raman spectroscopy (RS) is a powerful technique that permits the non-destructive chemical analysis of cells and tissues without the need for expensive and complex sample preparation. To date, samples have been routinely mounted onto calcium fluoride ( ... ...

    Abstract Raman spectroscopy (RS) is a powerful technique that permits the non-destructive chemical analysis of cells and tissues without the need for expensive and complex sample preparation. To date, samples have been routinely mounted onto calcium fluoride (CaF
    Language English
    Publishing date 2016-07-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1481008-6
    ISSN 1097-4555 ; 0377-0486
    ISSN (online) 1097-4555
    ISSN 0377-0486
    DOI 10.1002/jrs.4980
    Database MEDical Literature Analysis and Retrieval System OnLINE

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