WYMM: Birmingham

Birmingham, United Kingdom

Thursday 3rd October 2024, 10:00 - 17:00 GMT - Birmingham, United Kingdom (timings subject to change)

Generate ultra-rich data for answers with impact.

Who says you can’t see it all? With a comprehensive view of structural variants and methylation, nanopore technology powers the bigger and bolder research questions you’ve always wanted to ask.

Join us on Thursday 3rd October 2024 to hear from local experts who are breaking new ground in human genomics, using nanopore technology.

What you're missing matters. Stay on top of what's next.

Aside from talks ranging from human genomics for rare disease, to sequencing for cancer research, the full-day agenda will include networking breaks, Q&A, product displays, and opportunities to engage with your peers and nanopore experts.

Please note that this is an in-person event.

There is no delegate fee for this event, but registration is required. Lunch and refreshments will be provided. Your place at this event will be confirmed via email from events@nanoporetech.com.

Full agenda and venue details coming soon.

Agenda

Birmingham, United Kingdom
10:00 — 17:00 GMT	Agenda (subject to change)	Speaker
10:00 — 10:30	Registration and breakfast
10:30 — 11:00	Welcome	Rich Compton, Oxford Nanopore Technologies
11:00 — 11:35	The NanoporE Enhances Diagnosis in rarE Disease (NEEDED) study	Hannah Titheradge, Clinical Genetics at Birmingham Women's and Children's NHS Foundation Trust, United Kingdom Lorraine Hartles-Spencer, West Midlands Regional Genetics Lab, United Kingdom
11:35 — 12:00	Towards multi-modal liquid biopsy assays	Florent Mouliere, CRUK National Biomarker Centre, University of Manchester
12:00 — 13:30	Lunch
13:30 — 13:55	Oxford Nanopore Technologies Bioinformatics update	Dan Fordham, Oxford Nanopore Technologies
13:55 — 14:20	Differential isoform regulation in the human brain across regions, development, and between neuropsychiatric disorder cases and controls	Sofia Kudasheva, Earlham Institute
14:20 — 14:45	The era of complete human genomes	Cora Vacher, Oxford Nanopore Technologies
14:45 — 15:45	Networking session
15:45 — 16:15	Panel Q&A session	Moderated by Nirmala Santiapillai, Oxford Nanopore Technologies
16:15 — 16:50	Brain tumour classification using nanopore sequencing	Simon Deacon, University of Nottingham
16:50 — 17:00	Closing remarks	Oxford Nanopore Technologies
17:00 — 20:00	Drinks reception and networking

Speakers

Rich Compton, SVP, Sales & Commercial Operations, Oxford Nanopore Technologies
Richard joined Oxford Nanopore in 2016 to help build our commercial team from scratch. He is now responsible for the leadership of sales & commercial operations worldwide. Rich led Illumina’s EMEA Region, as Vice President and General Manager, prior to joining Oxford Nanopore.
Currently patients in England with monogenic developmental disorders will undergo NHS genetic testing including microarray and Whole Genome Sequencing (WGS) using short read sequencing (SRS) technology, with additional relevant genetic tests, such as methylation studies. Within this group a genetic diagnosis is made in about 30-40% of individuals. This means that a significant proportion of patients remain undiagnosed. We aim to evaluate the utility of Nanopore long read sequencing (LRS) as a tool to increase the diagnostic rate of suspected monogenic rare developmental disorders. Methods: We identified 28 individuals highly likely to have a monogenic disorder, who have no molecular genetic diagnosis, and have reached the ceiling of investigation within the NHS genomic medicine service. They were recruited as trios and quads (affected patient(s), and their parents) to Understanding the Genomic Basis for Human Disease (Ethics reference: 15/WM/0076, IRAS reference: 159499). Trio (or quad) WGS is performed using the Oxford Nanopore Promethion P24 instrument. We are using a range of existing software packages to study participants' genomes for potentially disease-causing variants including, sequence, copy number, methylation variants, and tandem repeats. Results: We have analysed the first 15 trio samples, identifying a diagnosis of Coffin Siris syndrome in one of these patients and identified the likely molecular cause of another family’s Familial Adenomatous Polyposis. We also will discuss the feasibility of implementation of Nanopore sequencing into clinical diagnostic testing pathway. Conclusion: Nanopore LRS has increased the diagnostic rate for patients with likely monogenic developmental disorders. Grants: Lifearc Pathfinder award and NIHR Research Scholarship

Currently patients in England with monogenic developmental disorders will undergo NHS genetic testing including microarray and Whole Genome Sequencing (WGS) using short read sequencing (SRS) technology, with additional relevant genetic tests, such as methylation studies. Within this group a genetic diagnosis is made in about 30-40% of individuals. This means that a significant proportion of patients remain undiagnosed. We aim to evaluate the utility of Nanopore long read sequencing (LRS) as a tool to increase the diagnostic rate of suspected monogenic rare developmental disorders. Methods: We identified 28 individuals highly likely to have a monogenic disorder, who have no molecular genetic diagnosis, and have reached the ceiling of investigation within the NHS genomic medicine service. They were recruited as trios and quads (affected patient(s), and their parents) to Understanding the Genomic Basis for Human Disease (Ethics reference: 15/WM/0076, IRAS reference: 159499). Trio (or quad) WGS is performed using the Oxford Nanopore Promethion P24 instrument. We are using a range of existing software packages to study participants' genomes for potentially disease-causing variants including, sequence, copy number, methylation variants, and tandem repeats. Results: We have analysed the first 15 trio samples, identifying a diagnosis of Coffin Siris syndrome in one of these patients and identified the likely molecular cause of another family’s Familial Adenomatous Polyposis. We also will discuss the feasibility of implementation of Nanopore sequencing into clinical diagnostic testing pathway. Conclusion: Nanopore LRS has increased the diagnostic rate for patients with likely monogenic developmental disorders. Grants: Lifearc Pathfinder award and NIHR Research Scholarship

Hannah Titheradge, Consultant, Clinical Genetics at Birmingham Women's and Children's NHS Foundation Trust, United Kingdom
Currently patients in England with monogenic developmental disorders will undergo NHS genetic testing including microarray and Whole Genome Sequencing (WGS) using short read sequencing (SRS) technology, with additional relevant genetic tests, such as methylation studies. Within this group a genetic diagnosis is made in about 30-40% of individuals. This means that a significant proportion of patients remain undiagnosed. We aim to evaluate the utility of Nanopore long read sequencing (LRS) as a tool to increase the diagnostic rate of suspected monogenic rare developmental disorders. Methods: We identified 28 individuals highly likely to have a monogenic disorder, who have no molecular genetic diagnosis, and have reached the ceiling of investigation within the NHS genomic medicine service. They were recruited as trios and quads (affected patient(s), and their parents) to Understanding the Genomic Basis for Human Disease (Ethics reference: 15/WM/0076, IRAS reference: 159499). Trio (or quad) WGS is performed using the Oxford Nanopore Promethion P24 instrument. We are using a range of existing software packages to study participants' genomes for potentially disease-causing variants including, sequence, copy number, methylation variants, and tandem repeats. Results: We have analysed the first 15 trio samples, identifying a diagnosis of Coffin Siris syndrome in one of these patients and identified the likely molecular cause of another family’s Familial Adenomatous Polyposis. We also will discuss the feasibility of implementation of Nanopore sequencing into clinical diagnostic testing pathway. Conclusion: Nanopore LRS has increased the diagnostic rate for patients with likely monogenic developmental disorders. Grants: Lifearc Pathfinder award and NIHR Research Scholarship

Currently patients in England with monogenic developmental disorders will undergo NHS genetic testing including microarray and Whole Genome Sequencing (WGS) using short read sequencing (SRS) technology, with additional relevant genetic tests, such as methylation studies. Within this group a genetic diagnosis is made in about 30-40% of individuals. This means that a significant proportion of patients remain undiagnosed. We aim to evaluate the utility of Nanopore long read sequencing (LRS) as a tool to increase the diagnostic rate of suspected monogenic rare developmental disorders. Methods: We identified 28 individuals highly likely to have a monogenic disorder, who have no molecular genetic diagnosis, and have reached the ceiling of investigation within the NHS genomic medicine service. They were recruited as trios and quads (affected patient(s), and their parents) to Understanding the Genomic Basis for Human Disease (Ethics reference: 15/WM/0076, IRAS reference: 159499). Trio (or quad) WGS is performed using the Oxford Nanopore Promethion P24 instrument. We are using a range of existing software packages to study participants' genomes for potentially disease-causing variants including, sequence, copy number, methylation variants, and tandem repeats. Results: We have analysed the first 15 trio samples, identifying a diagnosis of Coffin Siris syndrome in one of these patients and identified the likely molecular cause of another family’s Familial Adenomatous Polyposis. We also will discuss the feasibility of implementation of Nanopore sequencing into clinical diagnostic testing pathway. Conclusion: Nanopore LRS has increased the diagnostic rate for patients with likely monogenic developmental disorders. Grants: Lifearc Pathfinder award and NIHR Research Scholarship

Lorraine Hartles-Spencer, Principal Clinical Scientist, West Midlands Regional Genetics Lab, United Kingdom
Liquid biopsy and cell-free DNA have emerged as important biomarkers in oncology. Current approaches based on the sequencing of mutation or methylation markers recover a small fraction of events that makes cancer. Mining the multiple layers of omics (genomic, epigenomic, transcriptomic, fragmentomic) and analytes (cfDNA, cfRNA, extracellular vesicles) in blood samples from cancer patients have the potential to boost liquid biopsy and unlock new applications.

Liquid biopsy and cell-free DNA have emerged as important biomarkers in oncology. Current approaches based on the sequencing of mutation or methylation markers recover a small fraction of events that makes cancer. Mining the multiple layers of omics (genomic, epigenomic, transcriptomic, fragmentomic) and analytes (cfDNA, cfRNA, extracellular vesicles) in blood samples from cancer patients have the potential to boost liquid biopsy and unlock new applications.

Florent Mouliere, CRUK National Biomarker Centre, University of Manchester
Dan Fordham, Director, Strategic Product Management, EMEA, Oxford Nanopore Technologies
Dr. Dan Fordham is Director, Strategic Product Management EMEA at Oxford Nanopore Technologies focusing on delivering success to critical projects through integration, collaboration, and technical insight. He is also a committee member of the Genetics Society as a representative of Corporate Genetics and Biotechnology.
Cora Vacher, Associate Director, Segment Marketing, Oxford Nanopore Technologies
Cora Vacher is the Associate Director of Segment Marketing at Oxford Nanopore Technologies. Cora is passionate about genomics, in particular how genomics can help decipher and alleviate the burden of neurological diseases from neurodevelopmental to late onset neurodegenerative disorders. She came to the UK for a postdoctoral position on the genetic of Huntington’s disease in Cambridge and subsequently moved to commercial organisations.
Neurodevelopmental disorders (NDDs), including schizophrenia, are associated with dysregulated alternative splicing. However, NDD risk genes tend to be lowly expressed and have complex gene models making their isoform identification and quantification challenging with current approaches. This severely impedes the functional interpretation of their variation across tissues, and conditions. We applied CaptureSeq target enrichment coupled with Oxford Nanopore sequencing to characterise and quantify RNA isoform profiles of 1221 protein-coding and lncRNA genes across 52 human post-mortem brain samples: cortex, caudate, and hippocampus from 20 individuals (adult and fetal controls, and 12 adults with a neuropsychiatric diagnosis). We identified 44,624 unique isoforms (88.4% previously unannotated) and revealed 228 significant changes in isoform proportions (i.e. switches) between control adult brain regions, and 257 between adult and fetal cortex, with some switches predicted to impact the coding potential and protein structure. The previously overlooked brain isoform diversity and expression patterns provide us with an opportunity to characterise the functional implications of genetic variation associated with NDDs.

Neurodevelopmental disorders (NDDs), including schizophrenia, are associated with dysregulated alternative splicing. However, NDD risk genes tend to be lowly expressed and have complex gene models making their isoform identification and quantification challenging with current approaches. This severely impedes the functional interpretation of their variation across tissues, and conditions. We applied CaptureSeq target enrichment coupled with Oxford Nanopore sequencing to characterise and quantify RNA isoform profiles of 1221 protein-coding and lncRNA genes across 52 human post-mortem brain samples: cortex, caudate, and hippocampus from 20 individuals (adult and fetal controls, and 12 adults with a neuropsychiatric diagnosis). We identified 44,624 unique isoforms (88.4% previously unannotated) and revealed 228 significant changes in isoform proportions (i.e. switches) between control adult brain regions, and 257 between adult and fetal cortex, with some switches predicted to impact the coding potential and protein structure. The previously overlooked brain isoform diversity and expression patterns provide us with an opportunity to characterise the functional implications of genetic variation associated with NDDs.

Sofia Kudasheva, PhD Student, Earlham Institute
Nirmala Santiapillai, Oxford Nanopore Technologies
Carolyn Tregidgo, VP Applied Development, Oxford Nanopore Technologies
Carolyn Tregidgo is a technical leader with significant experience in DNA sequencing of rare disease and cancer genomes as well as product development of DNA sequencing technology. With a background in biophysics, Carolyn completed her PhD in fluorescence microscopy before joining Illumina where she worked on developing multiple sequencing platforms. Carolyn went on to join Genomics England where she led the bioinformatics delivery team responsible for integration of new pipeline developments and return of results. During her time at Genomics England she also managed the pipeline deployment to monitor severe response to covid-19 and oversaw the successful development of the Genomic Medicine Service. Carolyn joined Exact Sciences Innovation in 2020, formally Base Genomics, a spin out of Oxford University, where she was head of R&D. Since August 2023, she has been VP of Applied and Late-stage development at Oxford Nanopore Technologies where she is responsible for all regulated product development.
We present ROBIN, a tool based upon PromethION nanopore sequencing technology that can provide both real-time, intraoperative methylome classification and next-day comprehensive molecular profiling within a single assay. We believe that our tool is a significant step change in the ability to apply nanopore adaptive sampling to classification problems and treatment implementation in patients.

We demonstrate classifier performance on 50 prospective intraoperative cases within the context of an NHS pathology laboratory, achieving a sample preparation time under 2 hours and generating robust tumour classifications within minutes of sequencing. Furthermore, ROBIN can detect single nucleotide variants, copy number variants and structural variants in real-time, and is able to inform a complete molecular profile within 24 hours. This greatly improves upon current standard of care turnaround times, with a potentially transformative impact in clinical practice.

We present ROBIN, a tool based upon PromethION nanopore sequencing technology that can provide both real-time, intraoperative methylome classification and next-day comprehensive molecular profiling within a single assay. We believe that our tool is a significant step change in the ability to apply nanopore adaptive sampling to classification problems and treatment implementation in patients.

We demonstrate classifier performance on 50 prospective intraoperative cases within the context of an NHS pathology laboratory, achieving a sample preparation time under 2 hours and generating robust tumour classifications within minutes of sequencing. Furthermore, ROBIN can detect single nucleotide variants, copy number variants and structural variants in real-time, and is able to inform a complete molecular profile within 24 hours. This greatly improves upon current standard of care turnaround times, with a potentially transformative impact in clinical practice.

Simon Deacon, University of Nottingham