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  1. Article ; Online: A systematic review of biologically-informed deep learning models for cancer: fundamental trends for encoding and interpreting oncology data.

    Wysocka, Magdalena / Wysocki, Oskar / Zufferey, Marie / Landers, Dónal / Freitas, André

    BMC bioinformatics

    2023  Volume 24, Issue 1, Page(s) 198

    Abstract: Background: There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which ... ...

    Abstract Background: There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings.
    Methods: This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. It focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental properties in the biomedical domain. For this, we retrieved and analyzed 42 studies focusing on emerging architectural and methodological advances, the encoding of biological domain knowledge and the integration of explainability methods.
    Results: We discuss the recent evolutionary arch of DL models in the direction of integrating prior biological relational and network knowledge to support better generalisation (e.g. pathways or Protein-Protein-Interaction networks) and interpretability. This represents a fundamental functional shift towards models which can integrate mechanistic and statistical inference aspects. We introduce a concept of bio-centric interpretability and according to its taxonomy, we discuss representational methodologies for the integration of domain prior knowledge in such models.
    Conclusions: The paper provides a critical outlook into contemporary methods for explainability and interpretability used in DL for cancer. The analysis points in the direction of a convergence between encoding prior knowledge and improved interpretability. We introduce bio-centric interpretability which is an important step towards formalisation of biological interpretability of DL models and developing methods that are less problem- or application-specific.
    MeSH term(s) Humans ; Deep Learning ; Neoplasms/genetics ; Medical Oncology ; Biological Evolution ; Biology
    Language English
    Publishing date 2023-05-15
    Publishing country England
    Document type Systematic Review ; Journal Article
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/s12859-023-05262-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online: Active entailment encoding for explanation tree construction using parsimonious generation of hard negatives

    Bogatu, Alex / Zhou, Zili / Landers, Dónal / Freitas, André

    2022  

    Abstract: Entailment trees have been proposed to simulate the human reasoning process of explanation generation in the context of open--domain textual question answering. However, in practice, manually constructing these explanation trees proves a laborious ... ...

    Abstract Entailment trees have been proposed to simulate the human reasoning process of explanation generation in the context of open--domain textual question answering. However, in practice, manually constructing these explanation trees proves a laborious process that requires active human involvement. Given the complexity of capturing the line of reasoning from question to the answer or from claim to premises, the issue arises of how to assist the user in efficiently constructing multi--level entailment trees given a large set of available facts. In this paper, we frame the construction of entailment trees as a sequence of active premise selection steps, i.e., for each intermediate node in an explanation tree, the expert needs to annotate positive and negative examples of premise facts from a large candidate list. We then iteratively fine--tune pre--trained Transformer models with the resulting positive and tightly controlled negative samples and aim to balance the encoding of semantic relationships and explanatory entailment relationships. Experimental evaluation confirms the measurable efficiency gains of the proposed active fine--tuning method in facilitating entailment trees construction: up to 20\% improvement in explanatory premise selection when compared against several alternatives.
    Keywords Computer Science - Computation and Language ; Computer Science - Artificial Intelligence
    Subject code 006
    Publishing date 2022-08-02
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Technology clinical trials: Turning innovation into patient benefit.

    Royle, Jennifer K / Hughes, Andrew / Stephenson, Laura / Landers, Dónal

    Digital health

    2021  Volume 7, Page(s) 20552076211012131

    Abstract: Health care needs to continuously evolve and innovate to maintain the health of populations. Technology has the potential to enable better patient engagement and ownership, as well as optimise therapeutic interventions and data-science approaches to ... ...

    Abstract Health care needs to continuously evolve and innovate to maintain the health of populations. Technology has the potential to enable better patient engagement and ownership, as well as optimise therapeutic interventions and data-science approaches to facilitate improved health care decisions. Yet, to date, technological innovation has not resulted in the rate of change that could have been predicted from other sectors. This article discusses multiple reasons for this and proposes a newly tested and deployed solution: the technology clinical trial. The technology clinical trial methodology has been developed through working directly with patients, clinical and medical devicetrial experts. This approach enables researchers to use the complex environment of health care as an opportunity to transform the pace of innovation and create new care pathways. Instead of testing a single innovation, researchers can 'step back' and systematically review all areas of the patient's journey for potential optimization. Then integrate novel data science, technological advances, process updates, behavioural science, and patient engagement to co-create a streamlined multidisciplinary solution. As a result, this research has the potential for larger advances due to the emergent benefits that can arise when the individual elements work together as a whole. These potential benefits are then robustly tested, characterised and measured in the trial environment to ensure that future application of the innovative pathway is supported by the robust empirical data health care requires.
    Language English
    Publishing date 2021-04-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2819396-9
    ISSN 2055-2076
    ISSN 2055-2076
    DOI 10.1177/20552076211012131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Patient attrition in Molecular Tumour Boards: a systematic review.

    Frost, Hannah / Graham, Donna M / Carter, Louise / O'Regan, Paul / Landers, Dónal / Freitas, André

    British journal of cancer

    2022  Volume 127, Issue 8, Page(s) 1557–1564

    Abstract: Background: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that ... ...

    Abstract Background: Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment.
    Methods: A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 51 papers were reviewed spanning a 6-year period from 11 different countries.
    Results: In total, 20% of patients received treatment through the MTB process. Of those that did not receive treatment, the main reasons were no mutations identified (27%), no actionable mutations (22%) and clinical deterioration (15%). However, data were often incomplete due to inconsistent reporting of MTBs with only 55% reporting on patients having no mutations, 55% reporting on the presence of actionable mutations with no treatment options and 59% reporting on clinical deterioration.
    Discussion: As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data.
    MeSH term(s) Clinical Decision-Making ; Clinical Deterioration ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Precision Medicine
    Language English
    Publishing date 2022-08-08
    Publishing country England
    Document type Journal Article ; Systematic Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-022-01922-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Meta-analysis informed machine learning: Supporting cytokine storm detection during CAR-T cell Therapy.

    Bogatu, Alex / Wysocka, Magdalena / Wysocki, Oskar / Butterworth, Holly / Pillai, Manon / Allison, Jennifer / Landers, Dónal / Kilgour, Elaine / Thistlethwaite, Fiona / Freitas, André

    Journal of biomedical informatics

    2023  Volume 142, Page(s) 104367

    Abstract: Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown otherwise promising results in cancer treatment. When emerging, CRS could be identified ...

    Abstract Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown otherwise promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across patients. In this paper, we exploit these similarities using machine learning algorithms and set out to pioneer a meta-review informed method for the identification of CRS based on specific cytokine peak concentrations and evidence from previous clinical studies. To this end we also address a widespread challenge of the applicability of machine learning in general: reduced training data availability. We do so by augmenting available (but often insufficient) patient cytokine concentrations with statistical knowledge extracted from domain literature. We argue that such methods could support clinicians in analyzing suspect cytokine profiles by matching them against the said CRS knowledge from past clinical studies, with the ultimate aim of swift CRS diagnosis. We evaluate our proposed methods under several design choices, achieving performance of more than 90% in terms of CRS identification accuracy, and showing that many of our choices outperform a purely data-driven alternative. During evaluation with real-world CRS clinical data, we emphasize the potential of our proposed method of producing interpretable results, in addition to being effective in identifying the onset of cytokine storm.
    MeSH term(s) Humans ; Cell- and Tissue-Based Therapy ; Cytokine Release Syndrome/diagnosis ; Cytokines ; Immunotherapy, Adoptive/methods ; Receptors, Chimeric Antigen
    Chemical Substances Cytokines ; Receptors, Chimeric Antigen
    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2057141-0
    ISSN 1532-0480 ; 1532-0464
    ISSN (online) 1532-0480
    ISSN 1532-0464
    DOI 10.1016/j.jbi.2023.104367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Online: A systematic review of biologically-informed deep learning models for cancer

    Wysocka, Magdalena / Wysocki, Oskar / Zufferey, Marie / Landers, Dónal / Freitas, André

    fundamental trends for encoding and interpreting oncology data

    2022  

    Abstract: There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain ... ...

    Abstract There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings. This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. It focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental properties in the biomedical domain. For this, we retrieved and analyzed 42 studies focusing on emerging architectural and methodological advances, the encoding of biological domain knowledge and the integration of explainability methods. We discuss the recent evolutionary arch of DL models in the direction of integrating prior biological relational and network knowledge to support better generalisation (e.g. pathways or Protein-Protein-Interaction networks) and interpretability. This represents a fundamental functional shift towards models which can integrate mechanistic and statistical inference aspects. We introduce a concept of bio-centric interpretability and according to its taxonomy, we discuss representational methodologies for the integration of domain prior knowledge in such models. The paper provides a critical outlook into contemporary methods for explainability and interpretabiltiy used in DL for cancer. The analysis points in the direction of a convergence between encoding prior knowledge and improved interpretability. We introduce bio-centric interpretability which is an important step towards formalisation of biological interpretability of DL models and developing methods that are less problem- or application-specific.

    Comment: 25 pages, 5 figures
    Keywords Quantitative Biology - Quantitative Methods ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning
    Subject code 006
    Publishing date 2022-07-02
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Book ; Online: NLI4CT

    Jullien, Maël / Valentino, Marco / Frost, Hannah / O'Regan, Paul / Landers, Donal / Freitas, André

    Multi-Evidence Natural Language Inference for Clinical Trial Reports

    2023  

    Abstract: How can we interpret and retrieve medical evidence to support clinical decisions? Clinical trial reports (CTR) amassed over the years contain indispensable information for the development of personalized medicine. However, it is practically infeasible to ...

    Abstract How can we interpret and retrieve medical evidence to support clinical decisions? Clinical trial reports (CTR) amassed over the years contain indispensable information for the development of personalized medicine. However, it is practically infeasible to manually inspect over 400,000+ clinical trial reports in order to find the best evidence for experimental treatments. Natural Language Inference (NLI) offers a potential solution to this problem, by allowing the scalable computation of textual entailment. However, existing NLI models perform poorly on biomedical corpora, and previously published datasets fail to capture the full complexity of inference over CTRs. In this work, we present a novel resource to advance research on NLI for reasoning on CTRs. The resource includes two main tasks. Firstly, to determine the inference relation between a natural language statement, and a CTR. Secondly, to retrieve supporting facts to justify the predicted relation. We provide NLI4CT, a corpus of 2400 statements and CTRs, annotated for these tasks. Baselines on this corpus expose the limitations of existing NLI models, with 6 state-of-the-art NLI models achieving a maximum F1 score of 0.627. To the best of our knowledge, we are the first to design a task that covers the interpretation of full CTRs. To encourage further work on this challenging dataset, we make the corpus, competition leaderboard, website and code to replicate the baseline experiments available at: https://github.com/ai-systems/nli4ct

    Comment: EMNLP 2023 Camera-ready, 15 pages
    Keywords Computer Science - Computation and Language ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning
    Subject code 004
    Publishing date 2023-05-05
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Book ; Online: Encoding Explanatory Knowledge for Zero-shot Science Question Answering

    Zhou, Zili / Valentino, Marco / Landers, Donal / Freitas, Andre

    2021  

    Abstract: This paper describes N-XKT (Neural encoding based on eXplanatory Knowledge Transfer), a novel method for the automatic transfer of explanatory knowledge through neural encoding mechanisms. We demonstrate that N-XKT is able to improve accuracy and ... ...

    Abstract This paper describes N-XKT (Neural encoding based on eXplanatory Knowledge Transfer), a novel method for the automatic transfer of explanatory knowledge through neural encoding mechanisms. We demonstrate that N-XKT is able to improve accuracy and generalization on science Question Answering (QA). Specifically, by leveraging facts from background explanatory knowledge corpora, the N-XKT model shows a clear improvement on zero-shot QA. Furthermore, we show that N-XKT can be fine-tuned on a target QA dataset, enabling faster convergence and more accurate results. A systematic analysis is conducted to quantitatively analyze the performance of the N-XKT model and the impact of different categories of knowledge on the zero-shot generalization task.
    Keywords Computer Science - Computation and Language ; Computer Science - Machine Learning
    Publishing date 2021-05-12
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Book ; Online: SemEval-2023 Task 7

    Jullien, Maël / Valentino, Marco / Frost, Hannah / O'Regan, Paul / Landers, Donal / Freitas, André

    Multi-Evidence Natural Language Inference for Clinical Trial Data

    2023  

    Abstract: This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. ...

    Abstract This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.
    Keywords Computer Science - Computation and Language ; Computer Science - Artificial Intelligence ; Computer Science - Machine Learning
    Subject code 004
    Publishing date 2023-05-04
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Book ; Online: Metareview-informed Explainable Cytokine Storm Detection during CAR-T cell Therapy

    Bogatu, Alex / Wysocka, Magdalena / Wysocki, Oskar / Butterworth, Holly / Landers, Donal / Kilgour, Elaine / Freitas, Andre

    2022  

    Abstract: Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown promising results in cancer treatment. When emerging, CRS could be identified by the ... ...

    Abstract Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across patients. In this paper, we exploit these similarities using machine learning algorithms and set out to pioneer a meta--review informed method for the identification of CRS based on specific cytokine peak concentrations and evidence from previous clinical studies. We argue that such methods could support clinicians in analyzing suspect cytokine profiles by matching them against CRS knowledge from past clinical studies, with the ultimate aim of swift CRS diagnosis. During evaluation with real--world CRS clinical data, we emphasize the potential of our proposed method of producing interpretable results, in addition to being effective in identifying the onset of cytokine storm.
    Keywords Quantitative Biology - Quantitative Methods ; Computer Science - Machine Learning
    Subject code 610
    Publishing date 2022-06-20
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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