Managing Large-Scale Genomic Datasets and Translation into Clinical Practice

Summary Objective:To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain. Method: We provide a synopsis of the articles selected for the IMIA Yearbook 2014, from which we attempt to derive a synthetic overview of current and future activities in the field. A first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor evaluated independently the set of 1,851 articles and 15 articles were retained for peer-review. Results: The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded three excellent articles regarding data management and genome medicine. In the first article, the authors present VEST (Variant Effect Scoring Tool) which is a supervised machine learning tool for prioritizing variants found in exome sequencing projects that are more likely involved in human Mendelian diseases. In the second article, the authors show how to infer surnames of male individuals by crossing anonymous publicly available genomic data from the Y chromosome and public genealogy data banks. The third article presents a statistical framework called iCluster+ that can perform pattern discovery in integrated cancer genomic data. This framework was able to determine different tumor subtypes in colon cancer. Conclusions: The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on large-scale biological, genomic, and Electronic Health Records data. Indeed, there is a need for powerful tools for managing and interpreting complex data, but also a need for user-friendly tools developed for the clinicians in their daily practice. All the recent research and development efforts are contributing to the challenge of impacting clinically the results and even going towards a personalized medicine in the near future.

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Findings from the Section on Bioinformatics and Translational Informatics

Yearbook of Medical Informatics ◽

10.1055/s-0038-1641612 ◽

2016 ◽

Vol 25 (01) ◽

pp. 207-210

Author(s):

T. Lecroq ◽

H. Dauchel ◽

Keyword(s):

Large Scale ◽

Clinical Care ◽

Genomic Medicine ◽

Genomic Data ◽

Evaluation Process ◽

The Cancer Genome Atlas ◽

Sub Saharan Africa ◽

Health Domain ◽

Research Activities ◽

Translational Informatics

Summary Objectives : To summarize excellent current research and propose a selection of best papers published in 2015 in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. Method : We provide a synopsis of the articles selected for the IMIA Yearbook 2016, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,566 articles and the evaluation results were merged for retaining 14 articles for peer-review. Results : The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded four excellent articles focusing this year on data management of large-scale datasets and genomic medicine that are mainly new method-based papers. Three articles explore the high potential of the re-analysis of previously collected data, here from The Cancer Genome Atlas project (TCGA) and one article presents an original analysis of genomic data from sub-Saharan Africa populations. Conclusions : The current research activities in Bioinformatics and Translational Informatics with application in the health domain continues to explore new algorithms and statistical models to manage and interpret large-scale genomic datasets. From population wide genome sequencing for cataloging genomic variants to the comprehension of functional impact on pathways and molecular interactions regarding a given pathology, making sense of large genomic data requires a necessary effort to address the issue of clinical translation for precise diagnostic and personalized medicine.

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Bioinformatics Methods and Tools to Advance Clinical Care

Yearbook of Medical Informatics ◽

10.15265/iy-2015-026 ◽

2015 ◽

Vol 24 (01) ◽

pp. 170-173 ◽

Cited By ~ 2

Author(s):

T. Lecroq ◽

L. F. Soualmia ◽

Keyword(s):

Mass Spectrometry ◽

Large Scale ◽

Cancer Survival ◽

High Resolution Mass Spectrometry ◽

Clinical Care ◽

Evaluation Process ◽

Daily Practice ◽

High Coverage ◽

Research Activities ◽

Translational Informatics

Summary Objectives: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care.Method: We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. Results: The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. Conclusions: The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their daily practice. All the recent research and development efforts contribute to the challenge of impacting clinically the obtained results towards a personalized medicine.

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Findings from the Section on Bioinformatics and Translational Informatics

Yearbook of Medical Informatics ◽

10.15265/iy-2016-050 ◽

2017 ◽

Vol 26 (01) ◽

pp. 188-192 ◽

Cited By ~ 1

Author(s):

H. Dauchel ◽

T. Lecroq

Keyword(s):

Intelligent Systems ◽

Large Scale ◽

Cancer Genomics ◽

Clinical Care ◽

Evaluation Process ◽

Omics Data ◽

Health Domain ◽

Medical Genomics ◽

Research Activities ◽

Translational Informatics

Summary Objective: To summarize excellent current research and propose a selection of best papers published in 2016 in the field of Bioinformatics and Translational Informatics with applications in the health domain and clinical care. Methods: We provide a synopsis of the articles selected for the IMIA Yearbook 2017, from which we attempt to derive a synthetic overview of current and future activities in the field. As in 2016, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section coverage. Each section editor evaluated separately the set of 951 articles returned and evaluation results were merged for retaining 15 candidate best papers for peer-review. Results: The selection and evaluation process of papers published in the Bioinformatics and Translational Informatics field yielded four excellent articles focusing this year on the secondary use and massive integration of multi-omics data for cancer genomics and non-cancer complex diseases. Papers present methods to study the functional impact of genetic variations, either at the level of the transcription or at the levels of pathway and network. Conclusions: Current research activities in Bioinformatics and Translational Informatics with applications in the health domain continue to explore new algorithms and statistical models to manage, integrate, and interpret large-scale genomic datasets. As addressed by some of the selected papers, future trends would include the question of the international collaborative sharing of clinical and omics data, and the implementation of intelligent systems to enhance routine medical genomics.

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Findings from the Section on Bioinformatics and Translational Informatics

Yearbook of Medical Informatics ◽

10.1055/s-0037-1606501 ◽

2017 ◽

Vol 26 (01) ◽

pp. 188-191

Author(s):

H. Dauchel ◽

T. Lecroq

Keyword(s):

Intelligent Systems ◽

Large Scale ◽

Cancer Genomics ◽

Clinical Care ◽

Evaluation Process ◽

Omics Data ◽

Health Domain ◽

Medical Genomics ◽

Research Activities ◽

Translational Informatics

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From Genome Sequencing to Bedside

Yearbook of Medical Informatics ◽

10.1055/s-0038-1638852 ◽

2013 ◽

Vol 22 (01) ◽

pp. 175-177 ◽

Cited By ~ 1

Author(s):

L. F. Soualmia ◽

T. Lecroq

Keyword(s):

Genome Sequencing ◽

High Throughput Sequencing ◽

Health Management ◽

Complex Diseases ◽

Evaluation Process ◽

Blood Analysis ◽

Sequencing Technologies ◽

Research Activities ◽

Rare Gene ◽

Translational Informatics

Summary Objectives: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and evidence-based medicine. Method: We provide a synopsis of the articles selected for the IMIA Yearbook 2013, from which we attempt to derive a synthetic overview of current and future activities in the field. Three steps of selection were performed by querying PubMed and Web of Science. A first set of 5,549 articles was refined into a second set of 1,272 articles from which 15 articles were retained for peer-review. Results: The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded four excellent articles regarding the Human Genome and Medicine. Exploiting genomic data depends on having the appropriate reference annotation available. In the first article, the goal of the GENCODE Consortium is to produce and publish The GENCODE human reference gene set. As a result it is composed by merged manual and automatic annotations, which are frequently updated from public experimental databases. The quality of genome sequencing is platform-dependant. In the second article, a generic database independent from the sequencing technologies, Huvariome, can help to identify errors and inconsistencies in sequencing. To understand complex diseases of patients it will be of great importance to detect rare gene variants. This is the aim of the third study. Finally, in the last article, the plasma's DNA of healthy individual and patients suffering from cancer is compared. Conclusions: The current research activities attest to the continuous convergence of Bioinformatics and Medical Informatics for clinical practice. For instance, a direct use of high throughput sequencing technologies for patients could aid the diagnosis of complex diseases (such as cancer) without invasive surgery (such as biopsy) but only with blood analysis. However, ongoing genomic tests will generate massive amounts of data and will imply new trends in the near future: “Big Data” and smart health management.

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EBS Behaviour Immediately After Repository Closure in a Clay Host Rock: The HE-E Experiment (Mont Terri URL)

ASME 2011 14th International Conference on Environmental Remediation and Radioactive Waste Management, Parts A and B ◽

10.1115/icem2011-59288 ◽

2011 ◽

Cited By ~ 1

Author(s):

Irina Gaus ◽

Klaus Wieczorek ◽

Juan Carlos Mayor ◽

Thomas Trick ◽

Jose´-Luis Garcia` Sin˜eriz ◽

...

Keyword(s):

Thermal Conductivity ◽

Host Rock ◽

Large Scale ◽

Process Models ◽

Research Activities ◽

Hydraulic Behaviour ◽

Validation Experiment ◽

Engineered Barrier ◽

Mont Terri

The evolution of the engineered barrier system (EBS) of geological repositories for radioactive waste has been the subject of many research programmes during the last decade. The emphasis of the research activities was on the elaboration of a detailed understanding of the complex thermo-hydro-mechanical-chemical processes, which are expected to evolve in the early post closure period in the near field. It is important to understand the coupled THM-C processes and their evolution occurring in the EBS during the early post-closure phase so it can be confirmed that the safety functions will be fulfilled. Especially, it needs to be ensured that interactions during the resaturation phase (heat pulse, gas generation, non-uniform water uptake from the host rock) do not affect the performance of the EBS in terms of its safety-relevant parameters (e.g. swelling pressure, hydraulic conductivity, diffusivity). The 7th Framework PEBS project (Long Term Performance of Engineered Barrier Systems) aims at providing in depth process understanding for constraining the conceptual and parametric uncertainties in the context of long-term safety assessment. As part of the PEBS project a series of laboratory and URL experiments are envisaged to describe the EBS behaviour after repository closure when resaturation is taking place. In this paper the very early post-closure period is targeted when the EBS is subjected to high temperatures and unsaturated conditions with a low but increasing moisture content. So far the detailed thermo-hydraulic behaviour of a bentonite EBS in a clay host rock has not been evaluated at a large scale in response to temperatures of up to 140°C at the canister surface, produced by HLW (and spent fuel), as anticipated in some of the designs considered. Furthermore, earlier THM experiments have shown that upscaling of thermal conductivity and its dependency on water content and/or humidity from the laboratory scale to a field scale needs further attention. This early post-closure thermal behaviour will be elucidated by the HE-E experiment, a 1:2 scale heating experiment setup at the Mont Terri rock laboratory, that started in June 2011. It will characterise in detail the thermal conductivity at a large scale in both pure bentonite as well as a bentonite-sand mixture, and in the Opalinus Clay host rock. The HE-E experiment is especially designed as a model validation experiment at the large scale and a modelling programme was launched in parallel to the different experimental steps. Scoping calculations were run to help the experimental design and prediction exercises taking the final design into account are foreseen. Calibration and prediction/validation will follow making use of the obtained THM dataset. This benchmarking of THM process models and codes should enhance confidence in the predictive capability of the recently developed numerical tools. It is the ultimate aim to be able to extrapolate the key parameters that might influence the fulfilment of the safety functions defined for the long term steady state.

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Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

International Journal of Molecular Sciences ◽

10.3390/ijms22052659 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2659

Author(s):

Gianluca Costamagna ◽

Giacomo Pietro Comi ◽

Stefania Corti

Keyword(s):

Drug Discovery ◽

Drug Screening ◽

Neural Development ◽

Neurological Disorders ◽

Large Scale ◽

Three Dimensional ◽

Induced Pluripotent Stem Cell ◽

Cellular Level ◽

Complex Data ◽

Complex Data Sets

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.

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Progress in Research on Carbon Nanotubes Reinforced Cementitious Composites

Advances in Materials Science and Engineering ◽

10.1155/2015/307435 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 17

Author(s):

Qinghua Li ◽

Jintao Liu ◽

Shilang Xu

Keyword(s):

Carbon Nanotubes ◽

Large Scale ◽

High Strength ◽

Cementitious Composites ◽

Scale Production ◽

Multiwalled Carbon ◽

Factors Affecting ◽

Environment And Health ◽

Research Activities ◽

Major Factors

As one-dimensional (1D) nanofiber, carbon nanotubes (CNTs) have been widely used to improve the performance of nanocomposites due to their high strength, small dimensions, and remarkable physical properties. Progress in the field of CNTs presents a potential opportunity to enhance cementitious composites at the nanoscale. In this review, current research activities and key advances on multiwalled carbon nanotubes (MWCNTs) reinforced cementitious composites are summarized, including the effect of MWCNTs on modulus of elasticity, porosity, fracture, and mechanical and microstructure properties of cement-based composites. The issues about the improvement mechanisms, MWCNTs dispersion methods, and the major factors affecting the mechanical properties of composites are discussed. In addition, large-scale production methods of MWCNTs and the effects of CNTs on environment and health are also summarized.

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A Decision Support System for Public Funding of Experimental Development in Energy Research

Energies ◽

10.3390/en11061357 ◽

2018 ◽

Vol 11 (6) ◽

pp. 1357 ◽

Cited By ~ 3

Author(s):

Simon Hirzel ◽

Tim Hettesheimer ◽

Peter Viebahn ◽

Manfred Fischedick

Keyword(s):

Decision Support ◽

Decision Support System ◽

Support System ◽

Large Scale ◽

Public Funding ◽

Evaluation Process ◽

Decision Makers ◽

Market Failures ◽

Energy Research ◽

Experimental Development

New energy technologies may fail to make the transition to the market once research funding has ended due to a lack of private engagement to conclude their development. Extending public funding to cover such experimental developments could be one way to improve this transition. However, identifying promising research and development (R&D) proposals for this purpose is a difficult task for the following reasons: Close-to-market implementations regularly require substantial resources while public budgets are limited; the allocation of public funds needs to be fair, open, and documented; the evaluation is complex and subject to public sector regulations for public engagement in R&D funding. This calls for a rigorous evaluation process. This paper proposes an operational three-staged decision support system (DSS) to assist decision-makers in public funding institutions in the ex-ante evaluation of R&D proposals for large-scale close-to-market projects in energy research. The system was developed based on a review of literature and related approaches from practice combined with a series of workshops with practitioners from German public funding institutions. The results confirm that the decision-making process is a complex one that is not limited to simply scoring R&D proposals. Decision-makers also have to deal with various additional issues such as determining the state of technological development, verifying market failures or considering existing funding portfolios. The DSS that is suggested in this paper is unique in the sense that it goes beyond mere multi-criteria aggregation procedures and addresses these issues as well to help guide decision-makers in public institutions through the evaluation process.

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