Innovate Life Technology

Innovate Life Technology

MGI Tech Co., Ltd.

Microbial Detection
Total Solution
MGI sequencing platform
for pathogen fast identification

MGI Tech Co., Ltd.
Service & Support
MGI has accumulated rich experience in gene sequencing with an excellent team of scientists andengineers, who are committed to providing comprehensive technical support in each section: fromthe installation, testing and operation, training, maintenance to subsequent upgrades, as well as thelaboratory system construction, experiment scheme design and sequencing data analysis. You will
experience an unprecedented journey of sequencing.

Contact Us
Address.: Building 11, Beishan Industrial Zone, Yantian District, Shenzhen, China 518083
Email: MGI-service@genomics.cn
Website: en.mgitech.cn
Tel: 4000-966-988
LinkedIn: www.linkedin.com/company/mgi-bgi
Twitter: @MGI_BGIFor Research Use Only
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Version：2018.10

WechatMicrobial Detection
Total Solution
MGI sequencing platform
for pathogen fast identification

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Innovate Life Technology
MGI Tech Co., Ltd.

About us02

Microbiological Detection Total Solution

Overview

03

Applications

05

Our Advantages

06

MGI’s multi-omics platforms include genetic sequencing, mass spectrometry, and

MGI sequencing

07

medical imaging. Providing real-time, comprehensive, life-long solutions, its mission

MGI analysis software

08

MGI Tech Co., Ltd. (MGI), a subsidiary of BGI Group, is committed to enabling effec-

Table of Contents

tive and affordable healthcare solutions for all. Based on its proprietary technology,
MGI produces sequencing devices, equipment, consumables, and reagents to
support life science research, medicine and healthcare.

is to develop and promote advanced life science tools for future healthcare.

Our Solution

09

Hands-on operation

11

Automatic operation solution

12

Our Report

13

Case Study

14

Timeline of
MGI Microbial Solutions
MGI founded2015.11

BGISEQ-500 launchedglobally at ICG-10

2016.04.13

MGISEQ-2000, MGISEQ-200 and MGIFLP, the world’s
first Modular NGS Workstation launched at ICG-12

BGISEQ-50 entering Chinese CDC

2016.11

BGISEQ-50 launchedglobally at ICG-11

2017.04

2017.09

MGI and CURETIS (a German company) achieved
strategic cooperation to open a new era of genetic
diagnosis of infectious diseases

2017.112018.02

Memorandum about “Cooperation of China-Brazil Infectious Diseases
and Prevention Research Center” jointedly signed by Brazil FIOCRUZ
foundation, Shenzhen Third People's Hospital, MGI, Institute ofMicrobiology, Chinese Academy of Sciences and so on

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Overview

04

Microbiological Detection Total Solution

Traditional pathogen detection methods
Culture-based method

TOF-MS (Time-of-flight mass spectrometry)

Laborious, time-consuming.
Not suitable for unculturable pathogens.
Few positive results.

Need clonal isolates.

Immunoassay

PCR screening

Sensitivity and specificity issues.

Can only detect known pathogens andprone to assay specific limitations.

How to identify the pathogen that leads
to infectious disease?

Each method has its limitation and can only detect known pathogens.

Identification of pathogens is essential in the treatment of patientswith infectious diseases. Currently, the predominant techniques rely
on conventional microbiology approaches. However, traditional

MGI sequencing approach

methods often fail to identify mixed-pathogens in complex clinicalsamples, making the diagnosis and treatment of infection more

Sample(without culture)

challenging. Therefore, a rapid and precise pathogen detection
approach is important to understand and treat the infection.

The challenge of applying NGS technology topathogen detection
High-throughput sequencing technology empowers the large-scale
pathogen screening by generating large amounts of genomics data.
However, the tremendous amount of raw information requires awell-built database and efficient analysis tools to support accurate

Sampleidentification.

High-throughput sequencing
preparation

Step 1:Nucleotide extraction

Step 2:library preparation

Data analysis

Step 3:high-throughput sequencing

MGI sequencing technology for pathogen detection
MGI has developed a high-throughput sequencing platform integrated

Microbial identification reportwith a pathogen detection system. This innovative technology can
perform fast, accurate and comprehensive pathogen screening forclinical diagnosis. Moreover, MGI provides varies hardware devices
and compatible reagent kits for the system to support an extensive
range of pathogen testing.

24 hours from sample to result
Fast, accurate and comprehensive pathogen detection

Step 4:data analysis

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Applications

06

Our Advantages

MGI NGS platform supports massive screening on unknown
pathogens in human or animal infection and allows accurate
diagnosis and treatment. Its diverse applications are listed below:

Animal health

Agriculture

Travel health

Microbial detection total solution of MGI can perform massive unknown pathogen screening with rapid andprecise identification that accurately diagnose and aid treatment decisions. Importantly, our cutting-edge
NGS platform benefits routine clinical microbiological diagnosis.

Animal scienceand medicine

Food safety

PublichealthPublic healthcare

Prevention and control ofhuman and animal diseases

Independent platforms

No need for preliminary test

Fully-automated sample preparation system,high-throughput sequencing platform andvarious compatible reagent kits.

No culture needed. Solutions for a wide variety ofenvironmental or clinical samples (human or
animal blood, respiratory tract fluid, cerebrospinal
fluid and intestine).

Up-to-date microbial database

On-board analysis system

A comprehensive database of 20,000 microbial
genomics enabling massive screening at one
time.

Reliable data analysis at both nucleic acid andprotein levels.

Precision medicine

The MGI NGS platform allows detection of

Unculturable pathogens

Pathogens without time-consuming culture

Infection of a rare or new pathogen strain

Co-infection

Hard-to-detect dysbacteriosis

As a highly-integrated sequencing system, MGI sequencing platform provides quick and reliable data for
precise pathogen detection.

Streamlined workflow
24 hours from sample to result-all in one stop.

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Microbiological Detection Total Solution

08

MGI's microbial detection total solution isbased on the data generated byindependent high-throughput sequencing
platform, automated sample preparation
system, self-developed compatible
reagents, and self-developed rapid
identification system for pathogen

Automated sample preparation system
MGISP-100 automated sample preparation system integrates nucleic acidextraction and library preparation into one instrument, providing a fast, stable andhighly efficient workflow.

infection, which could realize fast,accurate and comprehensive microbial
detection.

Independently developed platforms

Nucleic Acid Extraction

Hybridization Capture andEnzymatic Reactions

PCR

Magnetic Bead Purification
and Fragment Selection

Library Pooling

DNB Preparation

Certification: CE, CB, cTUVus

MGI’s fully-integrated sequencing system enables NGS technology to support thereal-time diagnosis of infectious diseases.

Independently Developed Analysis Software
Genetic Sequencer
Pathogen Fast Identification System
Product Information

Product model

MGISEQ-200

MGISEQ-2000

Product feature

Efficient

Flexible

MGI has developed PFI (Pathogen Fast Identification) software with a
database containing the genetic information of nearly 20,000 microbes.
The integrated system can quickly generate analyses of microbial genome
information.

Flow cell

FCS

FCS

FCL

Lane/Chip

1 LANE

2 LANE

4 LANE

Output Model

MediumMediumHigh

Maximum Output/RUN

60 GB

165 GB

1080 GB

Average Effective Signal Point~ 300 M~ 550 M

~1800 M

Minimum Read Length

SE50

SE50

Maximum Read Length

PE100

PE150

Product Certification

CB,CE, cTUVus and EAC

Microbial Detection Throughput

up to 16;up to 32;16-96

Product features

Simple workflow

Species coverage

Comprehensive analysis

The instrument has automatic
analysis software to launch data
analysis and FASTQ files which arecompatible for secondary analysis.

In addition to human reference genome
sequence, the system collects information
about common animal reference sequencessuch as pig, goat, sheep, mice, rat, carp,
goose, chicken, duck, cow, cat, dog andrabbit. The feature enables comprehensive
analysis to identify host species.

MGI sequencers eliminate high backgroundor noisy sequencing signal to generatehighly accurate pathogen identification
using RNA transcriptome and DNA genomic
sequencing.

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Innovate Life Technology
MGI Tech Co., Ltd.

10

Our Solution

Product introduction
MGI-developed pathogen fast identification system integrates a supported server, database for data analysis,
and ZLIMS software for more than data management.

Database
The pathogen fast identification
system collects approximately 20,000
microbial genomic sequences (if thespecies has multiple reference
genomes, the information will also be
included) in the database which
supports rapid and precise detection.

Microbial classification

Species

Genus

Bacteria

3878

1058

Archaea

470

124

Viruses

7334

729

Fungi

7738

1929

Parasites

551

310

Workflow

MGI microbial detection total solution does not require sample culture and preliminary tests. Additionally, it canidentify microorganisms in environmental or clinical samples at one stop.

Raw data
Data
qualitycontrol

Removethe host

Remove the reads with low quality, adaptors and “N”

RNA (Host & microbial transcriptome)

DNA (Host & microbial genome)

Remove rRNA and host genome

Remove rRNA and host genome

1

2

3

4

5

Sample Collection
And Accession

Nucleic Acid Extraction
And Library Preparation

Sequencing
And Base-calling

Bioinformatics
Analysis

ReportNon-host data
Alignment with database and classification

Dataalignment

Basic information

QC result

Results of identification

1. Summary of RNA/DNA
classification
2. Identification of RNA/DNAInteractive “Genus & species” list
pie chartof identification
RNA vs DNA result

blood, throat swab
collection, phlegm,
bronchoalveolar
lavage fluid,
cerebrospinal fluid,feces and different
tissuessample collectionZLIMS

ZLIMS, a MGI laboratory information management software, supports tracking sequencing
runs, data generation and management. The pathogen fast identification system integrates
onboard ZLIMS to monitor run progress of sample collection, library preparation, sequencing
and launch automated data analysis.

RNA

RNA
metatranscriptome

DNA
cfDNA

DNA
metagenomics

MGISEQ-2000

Library construction

High-throughput
sequencing

Nucleic acid extraction

MGISEQ-200

Pathogen Fast
Identification System

Bioinformatics
analysis

ATCGATCGATCG

ATCGATCGATCGGACGCTTGAACA

Pathogen sequences
to be tested

TTACAACTGTAG
CCGATCGGACGTCCGATCGGACGT

ATGGTTCAATCC

Standand pathogen
sequences in datobase

ReportManage the details of each experiment stepManage the priority of each workflow
Effectively schedule all resources
Monitor sequencing quality and instrument information in real-time
Trace the whole workflow of experimental data
Support all kinds of biological information analysis process and report

The MGI pathogen fast identification system is highly versatile, providing solutions for a broad range of
detection with the customized panel at one stop.

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12

Hands-onoperation

Automatic
operation solution

Flexible and Comprehensive

Simple and Efficient

Offers the pathogen fast identification of various DNA/RNA sample from blood, throat swab collection,

Offers the pathogen fast identification of various DNA/RNA sample from blood, throat swab collection,phlegm, bronchoalveolar lavage fluid, cerebrospinal fluid, feces and different tissues.

phlegm, bronchoalveolar lavage fluid, cerebrospinal fluid, feces and different tissues. Fully-automated systemprovides a fast, convenient and efficient user experience for pathogen detection.

Sample source
Plasma/Blood/ throat swab collection, phlegm, bronchoalveolar

Step 1

Step 1

lavage fluid, cerebrospinal fluid, feces and different tissues

Nucleic acid extraction

Nucleic acid extraction

Extraction kit
MagPure Circulating DNA kitB

Sample source
Plasma/Blood/ throat swab collection, phlegm, bronchoalveolar
lavage fluid, cerebrospinal fluid, feces and different tissues

MGIEasy Magnetic beads Microbiome DNA extraction Kit

Extraction kit

MGIEasy Magnetic beads Viral DNA/RNA extraction Kit

MagPure Circulating DNA kitB
MGIEasy Magnetic beads Microbiome DNA extraction Kit
MGIEasy Magnetic beads Viral DNA/RNA extraction Kit

Nucleic acid source

Step 2Library construction

cfDNA or 150-250bp fragmented DNA
gDNA (mechanical fragmentation)

Step 2Library construction

Nucleic acid source
cfDNA or 150-250bp fragmented DNA

gDNA (enzymatic fragmentation)

gDNA (enzymatic fragmentation)

Total RNA

Total RNA

Library construction kit

Library construction kit

MGIEasy Cell-free DNA Library Prep Set

MGIEasy Cell-free DNA Library Prep Set

MGIEasy Universal DNA Library Prep Set

MGIEasy FS DNA Library Prep Set

MGIEasy FS DNA Library Prep Set

MGIEasy RNA Library Prep Set

MGIEasy RNA Library Prep Set

Step 3

Step 3High-throughput
sequencing

High-throughput
sequencing
MGISEQ-2000

MGISEQ-200

MGISEQ-2000

MGISEQ-200

High-throughput sequencing

High-throughput sequencing

MGISEQ-2000RS High-throughput Sequencing Set
MGISEQ-200RS High-throughput Sequencing Set

MGISEQ-2000RS High-throughput Sequencing Set
MGISEQ-200RS High-throughput Sequencing Set

Step 4

Step 4

Bioinformatics analysis

Bioinformatics analysis
Analysis software

Analysis software

Pathogen Fast Identification System

Pathogen Fast Identification System

Analysis serverof bioinformatics

Hands on time

MGISP-100

Automatic time

Analysis serverof bioinformatics

Hands on time

Automatic time

Our Report

The MGI sequencer automatically generates pathogen detection report in a short time
including two main sections：13

14

Case Study

The microbial detection total solution is to understand the diversity within samples by sequencing all nucleotidesof both host and microbes. This method does not require preliminary knowledge of pathogenic microbial
genomes and as such, can identify unknown pathogens in infectious disease. Importantly, the unique identification technique supports developing strategies to control and prevent human and animal infectious diseases.

General information
The system automatically removes low-quality
host/rRNA sequence in raw data and calculates
clean reads and qualified data.

Case 1 Identification of a novel or variant pathogen strain
Overview

A 4-year-old boy was hospitalized with clinical presentations ofhand-foot-and-mouth disease including fever and vesicular exanthema on
his hands, feet, oral mucosa, and anus for 1 week. The qRT-PCR results
revealed that the causative agent was HEV instead of EV71 or CVA16. To
further verify the pathogen, a stool sample was collected from the patient
for metagenomic sequencing.

Solution

The stool specimen was collected for Pathogen Fast Identification with
automated RNA isolation, library preparation and high-throughput sequencing.

ResultTen non-overlapping contigs were assembled after high-throughput
sequencing and verified by mapping to the genomes of three pathogens:human coxsackievirusA24, enterovirus96, and human poliovirus 1.
Primers were used to amplify the sequences and analsyis suggested that
all the contigs belonged to a consensus sequence of new strain EV-96. It
is the first time that metagenomic sequencing has been used to identify
an EV-96 strain as the cause of HFMD.

Paper

A novel Enterovirus 96 circulating in China
causes hand, foot, and mouth diseasepublished on Virus Genes on February 7th, 2017

Identification result
The system initially analyzes DNA/RNA level bycomparing the sample sequencing information to
the database of bacterial, viral, archaeal, fungal
and parasite genomes. Subsequently it generates a pathogen identification report shown as
the Venn diagram. The report includes both DNA
and RNA identification result and comparison of
DNA versus RNA result.

2.1 Summary

2.2 DNA identification

2.3 RNA identification

2.4 RNA vs DNA

Analysis server of bioinformatics

Innovate Life Technology
MGI Tech Co., Ltd.

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Case 2 Identification of co-infections

Overview

Solution

16

Case 3 Diagnosis of rare pathogen

A 26-year-old woman developed a mild respiratory illness on Jan.

Overview

28, 2017, but symptoms progressed to recurrent fever, cough, chills,

On August 20, 2018, A 42-year-old man was hospitalized after
presenting with symptoms of severe headache, fever of 38.4 °C,

expectoration, slight hemoptysis, muscle and joint pain in theand elevated CSF leukocyte and protein levels. 24 hours post-pre-following days. On February 3, the patient was hospitalized due to worsening symptoms of cyanotic lips, fever ofsentation, the patient spoke incoherently, had breathing difficulties,

39.3 °C, heart rate of 144 beats/ min and diagnosed with severe pneumonia with ARDS. She was treated withbecame comatose and was subsequently transferred to ICU.

antibiotics and antiviral therapies and then discharged on February 17. Blood and respiratory secretions were

Further examination by CT scan showed hydrocephalus and brain edema. Four days later, acollected during her hospitalization for pathogen testing. The screening results from bacteria and fungi

culture from cerebrospinal fluid samples showed negative results for bacteria and fungi,

culture-based test, G-test and GM-test were all negative. In addition, HIV, HBV, influenza viruses, SARS-CoV,therefore, to identify the pathogen, the sample was further analyzed using high-throughput

MERS- CoV and other coronaviruses were negative by ELISA and/or (RT-)PCR assays.

sequencing on August 31. Results were reported to clinicians 2 days later.

Solution

Pulmonary secretions from the patient were

The cerebrospinal fluid sample collected from thepatient was analyzed on the MGI sequencing platformusing the Pathogen Fast Identification workflow.

collected on the first day of hospitalization andanalyzed using metagenomic sequencing to
Analysis server of bioinformatics

determine the cause of infection.

ResultTwo respiratory viruses, HRV and HBoV
were identified in high abundance using
sequencing and confirmed by specific(RT-)qPCR assays and a report generated
to diagnose acute co-infection of HBoV1and HRV-C.
In this case, metagenomic sequencing

Equine infectious anemia virusEnterovirus A

HHV-5
(150)

Rhinovirus C(1309)

FaGmV
(283)

reads that identified as Naegleria fowleri, a rare amebic pathogen thatcan cause primary amebic menigioencephalitis (PAM).

Torque teno virus 10
WU Polyomavirus

Bocavirus(197)

Interestingly the results revealed a low level (0.0266%) of sequencing

Naegleria fowleri(N=65,658 Reads)

human: 92.7916%
Naegleria: 0.0266%
Bacteria: 0.005%
Fungi: 0.0165%

Read Depth

ResultViruses: 0%
Others: 3.7076%
Unclassified: 3.4527%

showed a significant advantage indetection of the causative agents ofsevere illness over traditional methods
such as culture, ELISA, PCR, etc.

Analysis server of bioinformatics

Total=2166

Figure B Viral reads distribution.
coverage(%):0.264363 mean_depth:15
Windows(1000dp) along Naegleria flowleri Genome

because prior knowledge was not

Paperassumed or required.

Naegleria: 0.3689%

Metagenomic analysis identified

Bacteria: 0.0689%
Fungi: 0.2291%
Viruses: 1e-04%
Others: 51.4348%

co-infection with human rhinovirus

Unclassified: 47.8982%

C and bocavirus 1 in an adultsuffering from severe pneumonia
Published on Journal of Infection in

Total Reads Distribution

Reads Distribution
without Huamm Host

March 2018
PAM caused by Naegleria fowleri infection is extremely rare in China but almost always fatal. The patient went to the Songkran Festivalprior to the onset of illness and may have come into contact with sewage. In this case, traditional methods failed to detect the pathogen,however, the MGI high-throughput sequencing platform successfully identified the rare pathogen.

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MGI Tech Co., Ltd.

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Case 4 Public health issue

Overview

Case 5 Diagnosis of animal disease

A 45-year-old male returning to China from Angola showed symptoms of Rift Valley fever including fever

A group of goats, infected with unknown pathogens developed scabby lesions around their lips, muzzle, andOverview(38.8 °C), chills, headache, arthralgia, anorexia and enervation on July 13 and was hospitalized forin their mouth. To efficiently control the unknown infection, throat swab samples from the affected goatstreatment. BGI assisted the Entry-exit Inspection and Quarantine of China to obtain a whole genome

were tested using MGI Pathogen Fast Identification system with a report generated within two days.

sequence of Rift Valley fever virus from the individual using NGS technology. As a result, BGI helped
identify, quarantine and treat the individual and prevent a local outbreak of RVF in China.
The throat swab samples from goats were processed

Solution
Solutionusing the MGI Pathogen Fast Identification system with

RVFV isolation and culture identification

automatic DNA and RNA sample extraction.

Analysis server of bioinformatics

were done in biosafety lab of Guangdong
Inspection and Quarantine Technology
Center. BGI laboratory performed

A large proportion of sequencing reads in both DNA

Resulthigh-throughput sequencing of the(64.2%) and RNA (44%) samples mapped directly to thesample to gather genomic information

Orf virus which associates closely with the clinicalabout RVFV.

ResultAnalysis server of bioinformatics

Virus classification

Alignment of the full genome sequence of
the RVFV isolate (named RVFV-Beijing
strain) revealed 100% identity of three

symptoms presented.

raw data

gene segments and 98% homologous toTable 1 The microorganism identification of DNA and RNA sample from goat swab

Subtype identification

Rank

Genomic assembly

RVFV Kakamas isolate in South Africa.

Evolutionary
analysis

Site polymorphism
distribution

Genetic variation analysis

Key siteanalysis

DNA

name of pathogenRNAreads number

relative abundance

reads number

relative abundance1

Orf_virus

35859364.20%

11311

44%

2

Pseudocowpox_ virus

26658

4.80%

650

2.50%

3

Bacillus_subtilis

3130

0.60%

518

2.00%

4

Pseudomonas_aeruginosa

2011

0.40%

217

0.80%

5

Staphylococcus_aureus

1158

0.20%

220

0.90%

Direct comparison of the obtained sequencing reads to reference genome of Orf virus genome
showed 86.7% identity, 87.6% average coverage and 200X depth. (see Figure below)

published on VIROLOGICA SINICA in June 2017
Reverse

50

0.2

25

0.4

Coverage

75

0.6

0.8

100

ref|NC_005336.1|

0

25

50

75

100

Sequencing depth frequence

For ward

Kb

0.0

Paper

800
600
400
200
0

0

100

200

300

400

Sequencing depth(X)125

Or f_virus

Fig.1 Alignment linear graph ofassembled sequence and viral genome

Fig.2 Average coverage of viral genome

Fig.3 Average sequencing depth of viral genome

To verify the result, a traditional PCR assay was then performed and showed positive confirmation of Orf virus.
The MGI sequencing technology is a highly accurate method for pathogen identification which aids in rapid diagnosis andtreatment of animal disease.