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

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.


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


§ 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


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



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


"

Your own classification and historical data

updated continuously""

"

External data harmonized and

updated quarterly""


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


© 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"


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 §  Filters: broad splice and exonic other than synonymous; "

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 §  Filters: broad splice and exonic other than synonymous; "


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 §  Filters: broad splice and exonic other than synonymous; "



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 [email protected] "by 5 pm EDT, Friday 8/15.


§ 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 [email protected] 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.