next generation sequencing – benefits for patients jo whittaker/ su stenhouse
TRANSCRIPT
Next Generation Sequencing – Benefits for Patients
Jo Whittaker/
Su Stenhouse
NGS – Benefits for Patients
What is Next Generation Sequencing?
What are the benefits for patients?
How will the benefits be realised?
What is Next Generation Sequencing?
Massively parallel sequencing
Genomic DNAFragmented library of small piecesall sequenced at same time
A__GT___G__A _T___G__A GT___G__A__ A__GT___G
A__GT___G__A
ACTGTAATGGCA
Whole genome sequence –consensus of aligned reads
Individual reads aligned to reference sequence
What is Next Generation Sequencing?
Massive sequence output possible Terabytes of data (1,000,000,000,000)
Highly scalable Lower output machine; fewer samples per run; faster
resultsexomes
‘targeted’ regions (eg disease specific ‘set’ of genes) High throughput machine
multiplex samples; target specific region to screen many samples for particular variant
whole genome sequence
What is Next Generation Sequencing?
Evolving technology
Illumina HiSeq 2000
Life Technologies SOLiD 4
Ion Torrent PGM
Illumina MiSeq
Pacific Biosciences RS
Roche 454 GS FLX
Roche GS Junior
and then there is the bioinformatics
What are the benefits for patients?
Would you like a copy of the results?
Help!
Help!
What are the benefits to patients?
Widely applicable technology variants in individual’s DNA vs ‘reference’ sequence may
identify
new disease genes – high diagnostic yield
increased efficacy of treatments
reduced deleterious/no response to treatments
preventative treatments
differentiation of disease subtypes
How will the benefits be realised?
Marcel Nelen & Joris Veltman, Marcel Nelen & Joris Veltman, Nijmegen…. we think whole-genome- or exome-based approaches are currently most
suited for diagnostic implementation in genetically heterogeneous diseases, initially to complement and later to replace Sanger sequencing, qPCR and genomic microarrays.
Establishing the pathogenicity of individual genetic variants remains a daunting task, requiring novel bioinformatic tools and high-throughput functional approaches……….
Pharmacogenomics. 2012 Apr;13(5):511-4.Genome and exome sequencing in the clinic: unbiased genomic
approaches with a high diagnostic yield.
David Goldstein & colleaguesDuke University
Highlighted two challenges in particularHighlighted two challenges in particular
First, in our experience, laboratory-based functional analysis is animportant part of the evaluation, and it remains unclear how this wouldbe incorporated into routine clinical application of NGS……
Second, this work required substantial manual interrogation of both sequence data andcandidate genes. Although variant calling procedures are continually improved and thereare likely to be routines developed to simplify the process of candidate identification, it seems likely that for the foreseeable future, some level of expert judgement willcontinue to be required to identify causal mutations from sequence data, which will contribute to the cost and time of this type of diagnostics.
JMG Online First, published on May 11, 2012 as 10.1136/jmedgenet-2012-100819Clinical application of exome sequencing in undiagnosed genetic conditions
Anna C Need, Vandana Shashi, Yuki Hitomi, Kelly Schoch, Kevin V Shianna, Marie T McDonald, Miriam H Meisler, David B Goldstein
What are the benefits for patients?
Sharon and Ozzy both had a ‘genome test’ –
looked at genes predisposing to serious illness
Ozzy’s results – ‘perfect’
Sharon’s results – already knew she was genetically predisposed to colon cancer (and has been affected)
She also carries a gene mutation predisposing to breast cancer
She opted for a bilateral mastectomy –at the moment cannot accurately predict if / whenshe would develop breast cancer
How will the benefits be realised?
We don’t need to work with ‘x’ology
We’ve got our own sequencer
Genetics is different
We want to set the test up - thereare only 22 other labs doing it
It’s a secret……
How will the benefits be realised?
Select new ‘best friends’
UKGTN Lab
Develop specialist knowledge – define your service’s unique strengths
Pathologist
OncologistCardiologist
Neonatologist
ObstetricianNephrologist
Endocrinologist
Bioinformaticist
How will the benefits be realised?
Collaboration Networking Developing standardised protocols Using standardised locus specification and variant
nomenclature Quality assuring sequencing processes Quality assuring data analysis processes Phenotype & genotype data sharing Providing equitable access to the right test for the
patient
What are the benefits for patients?
Higher diagnostic yield and more timely diagnosis
Research describing the course of a disease or development of a disorder may allow it to be more effectively treated or prevented
What are the benefits for patients?
Hopefully, more choices about how to live with or manage their disorder