LeadingEdgeGenomicServices&Solu5ons

Introduction of Novogene Bioinformatics Corporation

Noel Chen, Ph.D. VP of Business Development

noel.chen@novogene.com

Novogene Overview

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•  Foundedin2011

•  Rapidgrowtheachyear,now1000employees

•  Providinghigh-quality,next-gensequencingandbioinforma5csservicesinresearchandclinicalmarkets

•  CurrentlythelargestIlluminacustomerandtheonlyIlluminaIGNpartnerinChina

•  ThelargestsequencingcenterinChinaincapacity

•  PreparingforIPO

•  RevenuehassurpassedBGIinresearchmarketinChinarecently

Headquarters in Beijing

Worldwide Branches of Novogene

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Beijing

Tianjin

HK

UKUS

Est.2011

Est.2014

Founder and Chief Executive

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Dr. Ruiqiang Li • One of the world’s leading experts in genomics and bioinformatics • Best known for developing the software SOAP for ultra-fast sequence mapping, variation detection, and de novo genome assembly. • Prior experience

•  Vice President of BGI •  Principle Investigator at Peking University &

Peking/Tsinghua Center for Life Sciences • 70 publications (30 in Nature and Science series) that are cited over 12,000 times • PhD in Biology from University of Copenhagen

The Development of Novogene

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28 86

198

506

0

100

200

300

400

500

600

2011 2012 2013 2014

Employees

2011 2012 2013 2014

Revenue

Both revenue and number of employees more than doubled each year since our

founding.

1,000 Professional Employees

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Administration 8%

Sequencing 15%

Service & Support 25%

R & D 12%

Bioinformatics 40%

Doctorates 14%

Masters 61%

Bachelors 23%

Others 2%

Our focus: High quality service and customer satisfaction 75% of our employees have advanced degrees.

The Largest Sequencing Center in China

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Platform Read Length Q30 (Data Quality Guarantee)

HiSeq X 2×150 bp ≥80%

HiSeq 2500/2000 2×250 bp 2×125 bp ≥85% 1×50 bp ≥90%

HiSeq 4000 2×150 bp

≥80% MiSeq

2×300 bp 2×250 bp

NextSeq 500 2×75 bp 1×75 bp

Total Output/Month 234 Tb

Illumina’s Official Quality Guarantee

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Our data quality guarantee exceeds Illumina’s official guarantee. We are the only company providing this guarantee.

The Largest Sequencing Center in China

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Platform Read Length Novogene Q30 Guarantee

Average Q30 Delivered

Illumina Q30 Guarantee

10 HiSeq X 2×150 bp ≥80% 88.11% ≥75%

10 HiSeq 2500/2000

2×250 bp ≥80% 91.22% ≥80% 2×125 bp ≥85% 88.29% ≥80% 1×50 bp ≥90% 96.57% ≥80%

1 HiSeq 4000 2×150 bp ≥80% 90.10% ≥75%

4 MiSeq 2×300 bp - 75.20% ≥70%

- ≥75% 2×250 bp ≥80%

1 NextSeq 500 2×75 bp ≥80% 90.37% ≥80% 1×75 bp ≥80% 85.58% ≥80%

Total Output/Month 234 Tb

Our Human Whole Genome Sequencing Service

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Platform HiSeq X Ten

Read length 2×150 bp

Turnaround time 15 working days

Standard analysis Additional 8 working days

Advanced analysis upon request

Different Batch Flow Cell 1 Flow Cell 2 Output 972.0 G 943.2 G

Q30 90.30% 88.90%

Different Sample Sample 1 Sample 2 Raw Data 105.5 G 105.8 G

Mapping Ratio 99.90% 99.90% Effective Coverage 31.7 31.8

Service Parameter

Data Output and Quality

“I am extremely satisfied with the quality of the WGS results Novogene delivered.”

From customer Justin Loe, CEO of Full Genomes Corporation, Maryland, USA

Human Whole Genome Sequencing (WGS)

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Standard Bioinformatics Pipeline of WGS

Raw data

Clean data

Alignment

Annotation

CNV

Case Control Yes

SNP, InDel SV Somatic SNV Somatic InDel

Extensive Quality Controls

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DNA/RNA Preparation

Sequencing

Bioinformatics Analysis

Sample Received

Libraries Preparation

Data Delivery

Sample QC Report

Data Delivery

~5 days

~4 days

~3-12 days

~15 days

Library QC Report

Raw data QC Report

Data Report

Delivery Records

To ensure the accuracy and reliability of the sequencing data, Novogene strictly controls the quality of every step.

Workflow

Data Analysis on HPC (High Performance Computing) Platform

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DELL Computing Nodes Memory Size: 17 TB

Computing Power: 73 T flops

Storage: 3.2 PB

Data Type Data Analysis Capacity / Month Human Genome 360 Tb / 4000 samples

Exome 40 Tb / 8000 samples

Transcriptome

Products and Services Overview

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Life Science Research Services p  Human whole genome &

exome sequencing

p  Transcriptome sequencing

p  Plant and animal sequencing

p  Microbial sequencing

p  Bioinformatics analysis

Clinical Genetic Testing (China)

p  Cancer generic testing & risk

assessment

p  Cancer drug panel

p  ctDNA detection

p  NIPT

Service Portfolio for Global Researchers

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Whole Genome Sequencing •  Whole genome re-sequencing •  Whole exome sequencing •  Single-cell DNA sequencing •  Target region sequencing

Transcriptome Sequencing •  mRNA sequencing •  Single-cell RNA sequencing •  lncRNA sequencing •  Whole genome bisulfite sequencing

Microbial Genome Sequencing •  Microbial genome re-sequencing •  Microbial de novo sequencing •  Metagenomic sequencing •  16S/18S/ITS amplicon sequencing

Animal & Plant Genome Sequencing •  Animal & Plant re-sequencing •  Animal & Plant de novo sequencing •  Pan-genome re-sequencing •  Genotyping by Sequencing

Solutions for Human Disease Research

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Technology Focus

DNA Level RNA Level Epigenetics Single cell

•  WGS •  WES •  Target-seq •  Cancer panel

•  RNA-seq •  DGE •  Small RNA-seq •  LncRNA－seq

•  WGBS •  WGS •  WES •  RNA-seq •  LncRNA-seq

•  SNP／InDel／SV／CNV

•  Somatic mutations

•  Driver gene •  Clonal

evolution

•  Differentially expressed genes

•  Alternative splicing

•  Fusion gene •  LncRNA

•  Methylation analysis

•  Differential methylation region（DMR）

•  SNP／InDel／SV／CNV

•  Differentially expressed genes

•  Heterogeneity

Whole Exome Sequencing (WES)

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Platform HiSeq 4000

Exome Capture Agilent SureSelect V6 (58M) / V5

Read length 2×150 bp (longer reads with 20% more data than PE125)

Turnaround time 15 working days Standard anaylsis Additional 5 working days

Service Parameter (State-of-the-Art Platform)

Raw data

Clean data

Alignment

Annotation

InDel

Case Control Yes

SNP Somatic SNP Somatic InDel

Standard Bioinformatics Pipeline ExAC database--including 17 international exome databases for free

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Inherit Susceptibility Gene Screening NovoCRTM

Individual cancer panels

Multi-cancer testing

Personalized Cancer Therapy NovoPMTM

Tissue samples

Standard 47 genes

Professional 483 genes

ctDNA

Standard 40 genes

Professional 483 genes

•  NovoPM detects SNVs, indels, CNVs, fusions, and their relationships with cancer drugs to guide personalized cancer therapy.

•  NovoCR assesses an individual’s risk in developing cancer. •  We also offer custom panel service based on Agilent capture and HiSeq 4000.

Cancer Panel Solutions

RNA Sequencing

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Platform HiSeq 4000 Read length 2×150 bp

Turnaround time 15 working days Standard anaylsis additional 15 working days

Service Parameters

Novogene Advantages

• HiSeq paired-end 150 bp (longer reads)

Sequencing strategy

• Over 3,000 customer projects successfully completed

Rich experience

• Self-developed software (NovoFinder)--aim to find the genes you need

Bioinformatics analysis

RNA Sequencing Data Analysis

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Sequencing Data QCTotal RNA mRNA Library

Genome Available Genome Unavailable

Genome Mapping

Gene Structure Gene Expression

Alternative Splicing Antisense Transcripts

SNP & InDel Differential exon usage

Gene Expression Level Sample Correlation

Differential Expressed Genes GO/KEGG Enrichment

Transcriptome Assembly

Transcripts Sequence

Length Distribution Function Annotation

SNP & InDel

Long Non-coding RNA Sequencing

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Platform HiSeq 4000

Read length Paired-end 150 bp

Turnaround time 40 working days

Service Parameter Standard Bioinformatics Analysis (by an all PhD team)

Long non-coding RNA plays important regulatory functions. Our service enables researchers to simultaneously obtain information on mRNAs and lncRNAs.

Microbial Genome Sequencing

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Microbial Genome-

sequencing

Bacterial genomesequen

cing

Draft map

Fine map

Complete map

Re-sequencing

Draft map

Fine map

Re-sequencing

16S

18S

ITS

Fosmid,

plasmid

Mitochondria

Chloroplast

Virus

Meta-genomic

sequencing

Meta-survey

Fungal genome

sequencing

Small genome

sequencing

Amplicon sequencing

Meta sequencing

Platform: HiSeq PE 150 1000+ samples sequenced per month

Single Cell Sequencing

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}5——z$�\•  heterogeneity

≈

Why?

Germ cell

}5——z$�\•  heterogeneity

≈

Why?

Neurons

Stem cell Immune cell

Tumor cell(CTC)

Single Cell Sequencing

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• MALBAC for DNA, SMARTER for RNA Amplification technology

• 2 papers published (Nature & Science) Rich experience

• HiSeq X for human, HiSeq2500/4000 for other species

Sequencing strategy

Novogene Advantages

Customer Projects Completed in 2014

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Transcriptome Sequencing

Human Resequencing

Microbial Sequencing

Plant & Animal

resequencing

Plant & Animal de

novo sequencing

3122 3181

813

243 32

We Understand Science

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•  >100 published ar=cles with a total impact fact of 649 in just 4 years

•  34 patents in NGS and bioinforma=cs

•  Numerous ar=cles in submission

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Human preimplantation embryos and embryonic stem cells

Methods: Single Cell lncRNA+mRNA Seq

22,687 maternally expressed

genes detected, including

8,701 lncRNAs,

9,735 increased

than microarray

2,733 novel

lncRNAs discovered and many

are expressed in specific developmental stages

EPI cells and primary hESC

outgrowth have dramatically

different transcriptome, 1,498 genes

showing differential expression.

Grope samples: Ø Metaphase II oocyte, zygote, 2-cell, 4-cell, 8-cell, morula and late blastocyst at hatching stage; Ø 3-30 biology repeats per group; Ø 124 cells totally

Method: lncRNA+mRNA

HiSeq2000, PE100 20M-60M clean reads; 438 Gb data totally

n  Novogene Case 1

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Human Single Sperm Cells

Methods: Single Cell Whole Genome Sequencing

One Healthy Asian Male in late 40s

93 sperm:~1x

70x99 sperm

MALBAC

23% coverage

2.8 million SNP

2368 autosomal crossover events in the sperm cells; 26 .6 crossovers per cell on average

Constructed a genetic map of recombination of the individual

5% sperm were deteced having autosomal aneuploidy

6 sperm:~5x

43% coverage

1.4 million hetSNPs

n  Novogene Case 2

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allotetraploid cotton Genome DNA

Methods: de novo and Transcriptome Sequencing

n  Novogene Case 3 allotetraploid cotton

~96% of the estimated allotetraploid genome (total scaffold length

2.4/2.5 Gb) 265,279 contigs

(N50=34.0 kb) and 40,407 scaffolds

(N50=1.6 Mb)

RNA-seq

245x

97 samples(from different organ,

developmental Stages and adverse conditions)

contig N50 34Kbscaffold N50 1.6Mtotal length 2.43G

allotetraploid cotton evolutionary mechanism

and function of A-subgenome and D-

subgenome.

A branch of MYB genes family takes an

important role in the fiber development.

Many CESA genes got significant positive

selection function in domestication

De novo

De novo Sequencing Publications

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l  Brief Introduction Applying next-generation sequencing and state-of-the-art assembly algorithms make

the construction of pan-genome map feasible. Constructing genome maps for several

individuals provides unprecedented opportunities to investigate the detailed genetic

diversity at population level.

Pan-genome Sequencing

ATGCTACGGTAACCCTGATTGCAATG

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。。。 。。。

ATGCTACGGTAACCCTGATTGCAATG

ATGCTACGGTAACCCTGATTGCAATG

。。。 。。。

Ø Key Points

The pan-genome is a superset of all the genes in all the strains of a species. ：

ü  Core Genome: Containing genes present in all strains;

ü  Dispensable Genome: Containing genes present in two or more strains;

ü  Specific Gene: Specific to single strain.

Core genome

dispensable genome

specific genome

l  Pan-Genome Sequencing

Material selection and QC

Library Construction

Genome preliminarily assembly

Pan-genome Construction

Customized bioinformatics analysis

Gene Annotation

comparative genomics analysis

SNP/InDel/SV/CNV / novel sequence

Gene family analysis

Phylogenetic analysis

Co-linear analysis

Sample genome : 60X

Complex genome: 100X

230bp/500bp/2K /5K

Pan-genome analysis of soybean wild relatives（IF：39.08）

LeadingEdgeGenomicServices&Solu5ons

Organizations Collaborated with Novogene in 2014

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Look forward to your sincere cooperation !

Website: www.novogene.com

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