Interpreting Human Next-Gen Sequencing Data with the knoSYS® Platform by Ben Salisbury

Interpreting Human Next-Gen Sequencing
Data with the knoSYS® Platform"
Presenter: Ben Salisbury, PhD, SVP of Clinical Products"
The Human Genome !
Interpretation Platform!
The Human Genome !
Date: August 14, 2014"

© 2014 Knome, Inc.!
Questions"
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webinar, please enter them in the
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at the end.

Align"Call"Annotate"Filter"Classify"Report"
NGS informatics and interpretation infrastructure"
Flexible, fast
bioinformatics
2
Comprehensive,
customizable
annotation
3
Indication-specific
filtering, prioritization, and
interpretation
Bioinformaticians &
Technologists
Geneticists, Clinicians, &
Genetic Counselors
1

The knoSYS® System Overview"
§ End-to-end: reads to report
§ Flexible, fast, secure
§ Supports a multi-disciplinary
team
§ Ideal for translational and clinical
laboratories
§ Multiple configuration options
k100

knoSYS Bioinformatics"
1
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 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
2
Integrated
Reference Data
Draft/edit
report
"
Your own classification
and historical data
updated continuously"
"
"
External data
harmonized and
updated quarterly"
"

knoSYS in silico panels"
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
Draft/edit
report
3

Query
Targets
Parameters
Comparison mode
Panel
Panels and queries"
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.
Panel
Panel
Project
Query
Targets
Parameters
Comparison mode
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.

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; "
Query 3: Mendelian autosomal dominant
§ Target: all known genes causing autosomal dominant disease
reference frequency < 0.5%
Query 4+: One query per inheritance mode

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
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%

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; "
Query 3: Broad
§ Target: all 56 genes

The Human Genome !
Live Demo"

§ 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"
"

Process and interpret
3 samples for free"
Getting started…"
Send an email to jvionas@knome.com "
by 5 pm EDT, Friday 8/15.

What’s Next?"
§ 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.
www.knome.com
twitter.com/knome
info@knome.com
facebook.com/knomeinc
linkedin.com/company/knome-inc
617-715-1000

Questions"
If you have any questions, please
enter them in the GoToWebinar
pane.
Any questions we don’t get to will be
answered via email, individually.

Interpreting Human Next-Gen Sequencing Data with the knoSYS® Platform by Ben Salisbury

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Interpreting Human Next-Gen Sequencing Data with the knoSYS® Platform by Ben Salisbury