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  1. Article ; Online: Melvin is a conversational voice interface for cancer genomics data.

    Perera, Akila R / Warrier, Vinay / Sundararaman, Shwetha / Hsiao, Yi / Ghosh, Soumita / Kularatnarajah, Linganesan / Pitt, Jason J

    Communications biology

    2024  Volume 7, Issue 1, Page(s) 30

    MeSH term(s) Communication ; Neoplasms/genetics
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05688-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A year in statistics-the view from the trenches.

    Perera, Rafael / Oke, Jason / Fanshawe, Thomas R

    BMJ evidence-based medicine

    2020  Volume 25, Issue 3, Page(s) 81–82

    MeSH term(s) Biomedical Research
    Language English
    Publishing date 2020-01-07
    Publishing country England
    Document type Editorial ; Comment
    ISSN 2515-4478
    ISSN (online) 2515-4478
    DOI 10.1136/bmjebm-2019-111303
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Graph-pMHC: graph neural network approach to MHC class II peptide presentation and antibody immunogenicity.

    Thrift, William John / Perera, Jason / Cohen, Sivan / Lounsbury, Nicolas W / Gurung, Hem R / Rose, Christopher M / Chen, Jieming / Jhunjhunwala, Suchit / Liu, Kai

    Briefings in bioinformatics

    2024  Volume 25, Issue 3

    Abstract: Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug ... ...

    Abstract Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning. Here, we develop graph-pMHC, a graph neural network approach to predict pMHCII presentation. We derive adjacency matrices for pMHCII using Alphafold2-multimer and address the peptide-MHC binding groove alignment problem with a simple graph enumeration strategy. We demonstrate that graph-pMHC dramatically outperforms methods with suboptimal inductive biases, such as the multilayer-perceptron-based NetMHCIIpan-4.0 (+20.17% absolute average precision). Finally, we create an antibody drug immunogenicity dataset from clinical trial data and develop a method for measuring anti-antibody immunogenicity risk using pMHCII presentation models. Our model increases receiver operating characteristic curve (ROC)-area under the ROC curve (AUC) by 2.57% compared to just filtering peptides by hits in OASis alone for predicting antibody drug immunogenicity.
    MeSH term(s) Histocompatibility Antigens Class II/chemistry ; Peptides/chemistry ; Antigen Presentation ; Neural Networks, Computer
    Chemical Substances Histocompatibility Antigens Class II ; Peptides
    Language English
    Publishing date 2024-03-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbae123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Melvin is a conversational voice interface for cancer genomics data

    Akila R. Perera / Vinay Warrier / Shwetha Sundararaman / Yi Hsiao / Soumita Ghosh / Linganesan Kularatnarajah / Jason J. Pitt

    Communications Biology, Vol 7, Iss 1, Pp 1-

    2024  Volume 6

    Abstract: Despite large collections of cancer genomics data being openly available, the inability to quickly interrogate this information remains a barrier for researchers and oncologists. Here we present Melvin, an Amazon Alexa skill to explore cancer genomics ... ...

    Abstract Despite large collections of cancer genomics data being openly available, the inability to quickly interrogate this information remains a barrier for researchers and oncologists. Here we present Melvin, an Amazon Alexa skill to explore cancer genomics data through simple conversations.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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  5. Article ; Online: Mutational signature assignment heterogeneity is widespread and can be addressed by ensemble approaches.

    Wu, Andy J / Perera, Akila / Kularatnarajah, Linganesan / Korsakova, Anna / Pitt, Jason J

    Briefings in bioinformatics

    2023  Volume 24, Issue 6

    Abstract: Single-base substitution (SBS) mutational signatures have become standard practice in cancer genomics. In lieu of de novo signature extraction, reference signature assignment allows users to estimate the activities of pre-established SBS signatures ... ...

    Abstract Single-base substitution (SBS) mutational signatures have become standard practice in cancer genomics. In lieu of de novo signature extraction, reference signature assignment allows users to estimate the activities of pre-established SBS signatures within individual malignancies. Several tools have been developed for this purpose, each with differing methodologies. However, due to a lack of standardization, there may be inter-tool variability in signature assignment. We deeply characterized three assignment strategies and five SBS signature assignment tools. We observed that assignment strategy choice can significantly influence results and interpretations. Despite varying recommendations by tools, Refit performed best by reducing overfitting and maximizing reconstruction of the original mutational spectra. Even after uniform application of Refit, tools varied remarkably in signature assignments both qualitatively (Jaccard index = 0.38-0.83) and quantitatively (Kendall tau-b = 0.18-0.76). This phenomenon was exacerbated for 'flat' signatures such as the homologous recombination deficiency signature SBS3. An ensemble approach (EnsembleFit), which leverages output from all five tools, increased SBS3 assignment accuracy in BRCA1/2-deficient breast carcinomas. After generating synthetic mutational profiles for thousands of pan-cancer tumors, EnsembleFit reduced signature activity assignment error 15.9-24.7% on average using Catalogue of Somatic Mutations In Cancer and non-standard reference signature sets. We have also released the EnsembleFit web portal (https://www.ensemblefit.pittlabgenomics.com) for users to generate or download ensemble-based SBS signature assignments using any strategy and combination of tools. Overall, we show that signature assignment heterogeneity across tools and strategies is non-negligible and propose a viable, ensemble solution.
    MeSH term(s) BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Mutation
    Chemical Substances BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein
    Language English
    Publishing date 2023-09-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbad331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Spatial Transcriptomic Analysis of Focal and Normal Areas of Myocyte Disarray in Human Hypertrophic Cardiomyopathy.

    Laird, Jason / Perera, Gayani / Batorsky, Rebecca / Wang, Hongjie / Arkun, Knarik / Chin, Michael T

    International journal of molecular sciences

    2023  Volume 24, Issue 16

    Abstract: Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and only a few disease- ... ...

    Abstract Hypertrophic Cardiomyopathy (HCM) is a common inherited disorder that can lead to heart failure and sudden cardiac death, characterized at the histological level by focal areas of myocyte disarray, hypertrophy and fibrosis, and only a few disease-targeted therapies exist. To identify the focal and spatially restricted alterations in the transcriptional pathways and reveal novel therapeutic targets, we performed a spatial transcriptomic analysis of the areas of focal myocyte disarray compared to areas of normal tissue using a commercially available platform (GeoMx, nanoString). We analyzed surgical myectomy tissue from four patients with HCM and the control interventricular septum tissue from two unused organ donor hearts that were free of cardiovascular disease. Histological sections were reviewed by an expert pathologist, and 72 focal areas with varying degrees of myocyte disarray (normal, mild, moderate, severe) were chosen for analysis. Areas of interest were interrogated with the Human Cancer Transcriptome Atlas designed to profile 1800 transcripts. Differential expression analysis revealed significant changes in gene expression between HCM and the control tissue, and functional enrichment analysis indicated that these genes were primarily involved in interferon production and mitochondrial energetics. Within the HCM tissue, differentially expressed genes between areas of normal and severe disarray were enriched for genes related to mitochondrial energetics and the extracellular matrix in severe disarray. An analysis of the gene expression of the ligand-receptor pair revealed that the HCM tissue exhibited downregulation of platelet-derived growth factor (PDGF), NOTCH, junctional adhesion molecule, and CD46 signaling while showing upregulation of fibronectin, CD99, cadherin, and amyloid precursor protein signaling. A deconvolution analysis utilizing the matched single nuclei RNA-sequencing (snRNA-seq) data to determine cell type composition in areas of interest revealed significant differences in fibroblast and vascular cell composition in areas of severe disarray when compared to normal areas in HCM samples. Cell composition in the normal areas of the control tissue was also divergent from the normal areas in HCM samples, which was consistent with the differential expression results. Overall, our data identify novel and potential disease-modifying targets for therapy in HCM.
    MeSH term(s) Humans ; Transcriptome ; Heart Transplantation ; Tissue Donors ; Cardiomyopathy, Hypertrophic/genetics ; Muscle Cells
    Language English
    Publishing date 2023-08-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241612625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Unique venom proteins from

    Valles, Steven M / Oliver, Jason B / Addesso, Karla M / Perera, Omaththage P

    Toxicon: X

    2021  Volume 9-10, Page(s) 100065

    Abstract: The Solenopsis venom protein 2 transcript was amplified, sequenced, probed, and analyzed ... ...

    Abstract The Solenopsis venom protein 2 transcript was amplified, sequenced, probed, and analyzed from
    Language English
    Publishing date 2021-05-07
    Publishing country England
    Document type Journal Article
    ISSN 2590-1710
    ISSN (online) 2590-1710
    DOI 10.1016/j.toxcx.2021.100065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Granulocyte transfusion supportive care for prolonged cytopenias post CD19 CAR T cell therapy.

    Perera, Nilu / Baidya, Shoma / Weber, Nicholas / Mudie, Kari / Butler, Jason / Curley, Cameron / Henden, Andrea / Hunt, Stewart / Subramoniapillai, Elango / Tey, Siok-Keen / Kennedy, Glen A / Scott, Ashleigh P

    Transfusion

    2024  Volume 64, Issue 4, Page(s) 762–765

    MeSH term(s) Humans ; Immunotherapy, Adoptive ; Cytopenia ; Receptors, Chimeric Antigen ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Antigens, CD19 ; Granulocytes
    Chemical Substances Receptors, Chimeric Antigen ; Antigens, CD19
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Letter
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17793
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Author Correction: Structural basis for pre-tRNA recognition and processing by the human tRNA splicing endonuclease complex.

    Hayne, Cassandra K / Butay, Kevin John U / Stewart, Zachary D / Krahn, Juno M / Perera, Lalith / Williams, Jason G / Petrovitch, Robert M / Deterding, Leesa J / Matera, A Gregory / Borgnia, Mario J / Stanley, Robin E

    Nature structural & molecular biology

    2024  Volume 31, Issue 2, Page(s) 390

    Language English
    Publishing date 2024-01-09
    Publishing country United States
    Document type Published Erratum
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-024-01213-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 56: Show issues

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  10. Article ; Online: Effects of aging on cortical representations of continuous speech.

    Karunathilake, I M Dushyanthi / Dunlap, Jason L / Perera, Janani / Presacco, Alessandro / Decruy, Lien / Anderson, Samira / Kuchinsky, Stefanie E / Simon, Jonathan Z

    Journal of neurophysiology

    2023  Volume 129, Issue 6, Page(s) 1359–1377

    Abstract: Understanding speech in a noisy environment is crucial in day-to-day interactions and yet becomes more challenging with age, even for healthy aging. Age-related changes in the neural mechanisms that enable speech-in-noise listening have been investigated ...

    Abstract Understanding speech in a noisy environment is crucial in day-to-day interactions and yet becomes more challenging with age, even for healthy aging. Age-related changes in the neural mechanisms that enable speech-in-noise listening have been investigated previously; however, the extent to which age affects the timing and fidelity of encoding of target and interfering speech streams is not well understood. Using magnetoencephalography (MEG), we investigated how continuous speech is represented in auditory cortex in the presence of interfering speech in younger and older adults. Cortical representations were obtained from neural responses that time-locked to the speech envelopes with speech envelope reconstruction and temporal response functions (TRFs). TRFs showed three prominent peaks corresponding to auditory cortical processing stages: early (∼50 ms), middle (∼100 ms), and late (∼200 ms). Older adults showed exaggerated speech envelope representations compared with younger adults. Temporal analysis revealed both that the age-related exaggeration starts as early as ∼50 ms and that older adults needed a substantially longer integration time window to achieve their better reconstruction of the speech envelope. As expected, with increased speech masking envelope reconstruction for the attended talker decreased and all three TRF peaks were delayed, with aging contributing additionally to the reduction. Interestingly, for older adults the late peak was delayed, suggesting that this late peak may receive contributions from multiple sources. Together these results suggest that there are several mechanisms at play compensating for age-related temporal processing deficits at several stages but which are not able to fully reestablish unimpaired speech perception.
    MeSH term(s) Speech/physiology ; Auditory Perception ; Noise ; Speech Perception/physiology ; Acoustic Stimulation/methods
    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80161-6
    ISSN 1522-1598 ; 0022-3077
    ISSN (online) 1522-1598
    ISSN 0022-3077
    DOI 10.1152/jn.00356.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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