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The Human Genome !Interpretation Platform!
The Human Genome !Interpretation Platform!
Interpreting Human Next-Gen Sequencing Data with the knoSYS® Platform"
Presenter: Ben Salisbury, PhD, SVP of Clinical Products"Date: August 14, 2014"
© 2014 Knome, Inc.!
Questions"
If you have any questions during the webinar, please enter them in the GoToWebinar pane. We will answer as many as possible at the end.
© 2014 Knome, Inc.!
NGS informatics and interpretation infrastructure"
Flexible, fast bioinformatics
Comprehensive, customizable
annotation
2
Indication-specific filtering, prioritization, and
interpretation
3
Align" Call" Annotate" Filter" Report"Classify"
Bioinformaticians & Technologists
Geneticists, Clinicians, & Genetic Counselors
1
© 2014 Knome, Inc.!
§ End-to-end: reads to report
§ Flexible, fast, secure
§ Supports a multi-disciplinary team
§ Ideal for translational and clinical laboratories
§ Multiple configuration options
The knoSYS® System Overview"
hardware
k100
© 2014 Knome, Inc.!
Flexible, open system"§ UI for standard, production processing § Command-line operation for bioinformaticians § APIs for scripting the knoSYS software § Modular selection of align and call software
– E.g., BWA & GATK 3.2 vs. Isaac § Grid computing environment for parallel processing
knoSYS Bioinformatics"
1
Align" Call" Annotate" Filter" Report"Classify"
© 2014 Knome, Inc.!
knoSYS Annotation"
Structure"§ Reference
genome § Genes and
transcripts from Ensembl and RefSeq
Variation"§ dbSNP § COSMIC § NCBI Exome
Seq. Project § 1000 Genomes
Project
Association"§ ClinVar § HGMD-Pro § Human Phenotype
Ontology § Gene Ontology
Prediction"§ SIFT § PolyPhen-2 § PhastCons § PhyloP
Integrated Reference Data
2
Draft/edit report
Align" Call" Annotate" Filter" Report"Classify"
"
Your own classification and historical data
updated continuously""
"
External data harmonized and
updated quarterly""
© 2014 Knome, Inc.!
Organize tests into reusable, in silico panels:"§ Indication-specific or general § Roll many steps into one § Finely tunable § Version-controlled and reproducible § Encapsulates your lab’s expertise § Sharable
knoSYS in silico panels"
Draft/edit report
3
Align" Call" Annotate" Filter" Report"Classify"
© 2014 Knome, Inc.!Q
uery
Comparison mode
Parameters
Targets
Pane
l
Targets"§ Genome § Exome § Gene list § Transcript list § Coordinates § Etc.
Parameters"§ Variant types § Quality metrics § Coding effect § Reference freq. § Etc.
Comparison Mode"§ X-linked § Aut. recessive § Tumor-only § Case-Control § Etc.
Pane
l
Pane
l
Project
Que
ry
Comparison mode
Parameters
Targets
Sequence
Sequence
Sequence
§ Panel – An in silico investigation tool composed of targeted Queries. A panel can be broad or narrow, focused on discovery or existing knowledge, clinical or research oriented. Panels can be private or shared and version-controlled.
§ Query – A panel component that searches a set of genomic Targets for variants that satisfy a set of Parameters and a specified Comparison Mode.
Panels and queries"
© 2014 Knome, Inc.!
Panel example: Exome Explorer"Purpose: End a diagnostic odyssey or conduct a comprehensive screen
Query 1: Broad § Filters: broad splice and exonic other than synonymous; "
reference frequency < 1%
Query 2: Truncating mutations § Filters: narrow splice, non-sense, or frameshift indel; "
reference frequency < 1%
Query 3: Mendelian autosomal dominant § Target: all known genes causing autosomal dominant disease § Filters: broad splice and exonic other than synonymous; "
reference frequency < 0.5%
Query 4+: One query per inheritance mode
© 2014 Knome, Inc.!
Panel example: Long QT Syndrome"Purpose: Carefully target the 3 main LQTS genes to aid in the diagnosis of Long QT Syndrome!
Query 1: Broad § Targets: KCNQ1, KCNH2, SCN5A § Filters: broad splice and exonic other than synonymous; "
reference frequency < 0.5%
Query 2: Truncating § Filters: narrow splice, non-sense, or frameshift indel
Query 3: Likely pathogenic missense § Target: transmembrane regions of KCNQ1 and KCNH2 § Filters: missense; reference frequency = 0%
Query 4: VUS § Target: SCN5A and the remainder of KCNQ1 and KCNH2 § Filters: missense; reference frequency < 0.1%
© 2014 Knome, Inc.!
Panel example: ACMG Incidental Findings"Purpose: Identify mutations in the 56 ACMG-recommended Incidental Findings genes!
Query 1: Known pathogenic § Target: variants with a “Pathogenic” assessment in ClinVar, etc.
Query 2: Expected pathogenic § Target: genes with “Expected Pathogenic” recommendation § Filters: narrow splice, nonsense, or frameshift indel; "
reference frequency < 0.5%
Query 3: Broad § Target: all 56 genes § Filters: broad splice and exonic other than synonymous; "
reference frequency < 1%
© 2014 Knome, Inc.!
§ Software only – The knoSYS software "can be installed on an organization’s "existing, high-performance hardware.
§ k25 – For labs that focus on targeted panels or moderate number of whole genomes, the k25 hardware is a low-cost entry solution for genomic interpretation.
§ k100 – The k100 is a high-performance, scalable, computing cluster with a database server and storage units.
§ Hosted – Either hardware model can also be hosted at a secure facility and accessed remotely.
Configuration options"
"Pay-per-sample
or License options available"
"
© 2014 Knome, Inc.!
Process and interpret 3 samples for free"
Getting started…"
Send an email to jvionas@knome.com "by 5 pm EDT, Friday 8/15.
© 2014 Knome, Inc.!
§ A recording of this webinar and the slides will be available on our website on Monday.
§ Stay up-to-date on upcoming webinars and events on our website.
What’s Next?"
www.knome.com twitter.com/knome info@knome.com facebook.com/knomeinc linkedin.com/company/knome-inc 617-715-1000
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