Tutorial: Nautilus LIMSIncreases Productivity inAventis LabHenry W. Long, Ph.D., RichardNewcombe, and Adrian Fergus

T he experiences of the Aventis

Cambridge Genomics Center

(ACGC; Cambridge, MA) in

implementing LIMS that incorporates

Web-based technologies, in order to

increase throughput, enhance produc-

tivity, and optimize research lab

processes, may be a useful pointer as to

what lies ahead.

The Drug Innovation and Approval

(DI&A) organization is the global

research division of Aventis (Strasbourg,

France). To improve the productivity and

efficacy of the lead generation process

within DI&A, the company formed sev-

eral of what it dubbed as High Perform-

ing Units (HPUs) to optimally apply

technology and create and disseminate

knowledge within the organization.

These HPUs were tasked with increasing

the efficiency and output of their respec-

tive activities within the drug discovery

process. As part of this process, laboratory

automation and data management have

been a major focus.

Aventis’ Molecular Genomics HPU is

located at ACGC. The activities of this

unit encompass a variety of laboratory

functions, including DNA sequencing,

cloning, transcriptional profiling, and

the management of a global clone repos-

itory, all of which support Aventis major

research sites in France, Germany, and

the U.S.

To meet the challenges of laboratory

information management across mul-

tiple platforms at the HPU, increase

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D a i l y B i o t e c h U p d a t e s . . . w w w . g e n e n g n e w s . c o m

Volume 24, Number 1January 1, 2004

Web-Based LIMS Platform Boosts ThroughputB I O B Y T E S

Thermo Electron’s Nautilus LIMS has been deployed to support laboratory processes,including the tracking of samples and projects, and management of the inventory of chips.

productivity, allow transparency, and

coordinate activities supporting Aventis’

multinational research organization, the

HPU implemented Thermo Electron’s

(Waltham, MA) Nautilus™ as the stan-

dard LIMS to support appropriate labo-

ratory processes. Nautilus is a flexible,

stable, commercial product designed to

be tailored to individual laboratory needs

by configuring workflow, and offers the

option of custom extensions.

To enhance the value of the LIMS,

Web interfaces have been deployed to

provide access to critical information for

all Aventis researchers via an intranet

site. To date, Nautilus has been config-

ured and deployed to operate in two key

areas at the ACGC. Work is ongoing to

install the LIMS in other related Aventis

facilities around the world, and new

enhancements are being evaluated for

existing systems.

Transcript-Profiling LIMS

The ACGC uses transcript-profiling

techniques to measure, both qualitatively

and quantitatively, gene expression levels

for numerous target-discovery and com-

pound-advancement applications.

Currently, Affymetrix’ (Santa Clara,

CA) GeneChip® platform is the primary

technology used at Aventis for genome-

wide profiling in target-identification

experiments. As a result of considerable

configuration, Nautilus is used to track

samples from receipt, generate standard

operating procedure reports, and manage

the inventory of chips.

The implementation has reportedly

led to significant improvements in labo-

ratory throughput, with no increase in

the number of research associates. It is

estimated that the costs saved by not hir-

ing extra associates to gain this increase

in throughput, added to the costs saved

by eliminated chip waste, has equaled

the investment made in the system, after

only 15 months.

Between 2001 and 2002, the HPU

reports, it was able to double the number

of chips processed by adding additional

hybridization stations and scanners, to

meet growing research needs at Aventis.

Features of the transcript-profiling

LIMS include the following:

•The Affymetrix GeneChip invento-

ry system, designed to allow accurate

tracking of chips, their association with

projects, and their expiration dates

using barcodes. This is a custom exten-

sion to Nautilus.

• Integration of the LIMS with the

Agilent 2100 Bioanalyzer, for RNA qual-

ity control; this allows automated sam-

ple routing based on numeric results of

the scan.

•Web portal for sample and project

tracking, designed for ease of navigation

and created to make the operation of the

transcript-profiling group transparent

across a global organization. This was

done by wrapping simple database

queries with Java Webpages.

•Quality-control (QC) data, generat-

ed for each chip with an in-house scan

QC analysis program, routed back to

Nautilus for further analysis through a

standard Nautilus interface or a direct

connection to SpotFire (Somerville,

MA) decision analytics from the LIMS.

In addition to these features, config-

urable, extensive reporting has proven

valuable in monitoring performance,

data sharing, and enabling laboratory

personnel and management to track

multiple samples and project progression

in parallel.

Global-Cloning LIMS

The ACGC and an HPU satellite site in

Frankfurt, Germany, conduct full-length

cloning, partial-domain cloning, and

recombinant cloning, all of which are

supported by Nautilus and a version of

Tasmania™, Thermo Electron’s middle-

ware Web application. Nautilus was con-

figured to support cloning pipelines,

including oligo design, PCR, sequencing,

finishing, and recombinant cloning. Tas-

mania is designed to assist development

and delivery of novel integrated applica-

tions using Web-based technologies.

A global solution has been created for

Aventis researchers located in Germany,

France, and the U.S., to register gene/

vector requests via a Web-based system

using the Tasmania architecture and

Nautilus. Developed in Java, the Web-

page communicates with the Nautilus

database and the Nautilus XML proces-

sor through simple object-access proto-

col messages using n-tier Web services

architecture.

At the center of this architecture is an

Internet Information Services Web server

and two drivers, which form the basis of

Tasmania. These drivers include a Nau-

tilus SQL Query driver that communi-

cates LIMS workflow information, such

A user-friendly Web interface allowsAventis researchers to register cloningrequests directly into the LIMS.

as sample attributes and predefined

vocabulary lists.

The Nautilus XML Processor Interface

driver communicates with the LIMS-

application functionality and has the

ability to register cloning requests direct-

ly into the LIMS. Information is returned

to the requestor in terms and format

designed to be easily understood by the

researcher. The solution also includes an

automated e-mail notification to the

requester and management personnel.

Requestors are also able to check the

status of their requests online and pro-

duce a final clone report, which includes

the clone history and all annotation

available in the LIMS.

Management in the Aventis cloning

section estimates that the amount of time

required to approve a request is now less

that half what it was before, saving sever-

al hours per week and allowing research

associates to concentrate on lab work and

not paperwork. This phase of the project

became operational in April 2003.

In August 2003, all phases of the

Cloning LIMS project became opera-

tional, including a new high-throughput

plate-based cloning pipeline for ACGC,

and a custom-cloning pipeline for the

cloning lab based in Frankfurt. The latter

involved building new extensions in

Nautilus for interfacing with a custom

database to support a sequencing labora-

tory that is also located in Frankfurt.

The latest phase of the Aventis LIMS

Project is a rollout of Nautilus to the

company’s DSE toxicogenomics facility

in Bridgewater, NJ. This new project will

entail enhancement of LIMS workflows

developed during the original Tran-

scriptome-Analysis project at ACGC,

plus the addition of new study-manage-

ment functionality.

Summary

The challenge of improving lab pro-

ductivity through increased automation

looks set to remain a constant reality.

Through the deployment of Thermo

Electron’s flexible, extensively config-

urable Nautilus LIMS using Web services

architecture, Aventis Cambridge Genom-

ic Center reports that it is experiencing

some success in relieving these pressures,

while also optimizing the value of data

that is generated.

Secure Web-based technologies pro-

vide one answer to allowing access to data

to those who need it, while providing

transparency within ACGS’ operations.

Extensive reporting capabilities cou-

pled with the data storage supplied by the

LIMS facilitate the gathering and sum-

marizing of relevant sample information

for the ACGC, which is working to effec-

tively accelerate current and future initia-

tives by benefiting from the work of ear-

lier projects.

Henry W. Long, Ph.D., is head of molecular genomicsHPU, and Richard Newcombe is lab manager forautomation, at Aventis Cambridge Genomics Center(Cambridge, MA).

Adrian Fergus works in international marketing atThermo Electron, Informatics and Services. Phone: +44161 942 3000. E-mail: info@thermoinformatics.com.Website: www.thermo.com/informatics.

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