Benefits for children with suspected cancer from routine whole-genome sequencing

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.</p

A reproducibility study of deep and surface machine learning methods for human-related trajectory prediction

In this paper, we compare several deep and surface state-of-the-art machine learning methods for risk prediction in problems that can be modelled as a trajectory of events separated by irregular time intervals. Trajectories are the abstract representation of many real-life data, such as patient records, student e-tivities, online financial transactions, and many others. Given the continuously increasing number of machine learning methods to predict future high-risk events in these contexts, we aim to provide more insight into re-producibility and applicability of these methods when changing datasets, parameters, and evaluation measures. As an additional contribution, we release to the community the implementations of all compared method

Towards Integrative Machine Learning and Knowledge Extraction

The BIRS Workshop \u201cAdvances in Interactive Knowledge Discovery and Data Mining in Complex and Big Data Sets\u201d (15w2181), held in July 2015 in Banff, Canada, was dedicated to stimulating a cross-domain integrative machine-learning approach and appraisal of \u201chot topics\u201d toward tackling the grand challenge of reaching a level of useful and useable computational intelligence with a focus on real-world problems, such as in the health domain. This encompasses learning from prior data, extracting and discovering knowledge, generalizing the results, fighting the curse of dimensionality, and ultimately disentangling the underlying explanatory factors in complex data, i.e., to make sense of data within the context of the application domain. The workshop aimed to contribute advancements in promising novel areas such as at the intersection of machine learning and topological data analysis. History has shown that most often the overlapping areas at intersections of seemingly disparate fields are key for the stimulation of new insights and further advances. This is particularly true for the extremely broad field of machine learning

Benefits for children with suspected cancer from routine whole-genome sequencing.

Acknowledgements: We thank S. Wakeling (Alice’s Arc), J. Miles (East Genomics Laboratory Hub), A. Sosinsky (Genomics England), P. Moss (Genomics England), A. Maartens (science writer, Wellcome Sanger Institute), G. Collord (University College Hospitals, London) and T. Treger (Wellcome Sanger Institute) for the discussion regarding the paper. We thank the scientific, technical and administrative staff of the North Thames and East Genomic Laboratory Hubs for making WGS possible. We acknowledge funding from the Wellcome Trust (personal fellowship to S. Behjati, institutional grant to the Wellcome Sanger Institute; references 220540/Z/20/A and 223135/Z/21/Z), the Pessoa de Araujo family (personal fellowship to A.H.) and NIHR (academic clinical fellowship to S.M.L.). This research was supported by the NIHR GOSH Biomedical Research Centre and NIHR Cambridge Biomedical Research Centre (NIHR203312). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. We are indebted to the children and families who participated in this study.Funder: NIHR Cambridge Biomedical Research Centre (NIHR203312)Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazilian Federal Agency for the Support and Evaluation of Graduate Education); doi: https://doi.org/10.13039/501100002322Funder: The Pessoa de Araujo family - Personal Fellowship to Dr Angus HodderFunder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: NIHR GOSH Biomedical Research CentreClinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care