From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “Startup brings RNA sequencing into the age of big data”

From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH)

6.29.22
Cécilia Carron

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EPFL spin-off Alithea Genomics has developed a system that allows scientists to easily tag bulk RNA samples with molecular barcodes so they can be processed by the hundreds in one single tube. The technology promises to dramatically shorten and streamline sample preparation for RNA sequencing, which will enable new applications for this technology, such as biomarker discovery and drug development.

RNA sequencing is becoming a key part of the process of developing new drugs and discovering biomarkers which indicate the presence of certain diseases. Armed with a snapshot of RNA strands – the messengers that carry DNA information – scientists can gradually decode intracellular “language”, detect anomalies and learn how to repair them. In order to extract insightful statistics, train artificial intelligence systems to identify abnormalities, and fast-track R&D, a new approach is needed – one that enables the generation of “big RNA data”, so that the functional state of thousands of samples can be profiled and compared simultaneously, at a fraction of the time and cost.

That’s where the technology developed by EPFL spin-off Alithea Genomics comes in. It “tags” RNA strands from hundreds of samples, allowing them to be analyzed in one single tube, instead of hundreds of tubes! This process is 25 times cheaper than conventional methods and reduces the time needed to sequence hundreds of samples from several days to just a few hours. The startup, which currently employs seven people and raised CHF 1 million in May this year, is preparing to launch new products and upscale manufacturing.

Using barcodes to cut RNA sequencing times

Next-generation sequencing has long been used to analyze DNA but is trickier to apply to RNA. This method involves combining samples from multiple sources and sequencing them in a single pass, saving both time and money. One of the key steps in this high-speed process is the preparation of a genomic library. At this stage, barcodes – short, predetermined sequences of DNA – are added to identify fragments belonging to the same group. Then, once the fragments have been analyzed, they can be reassigned to the correct sample using a special software program. This system works in much the same way as an airport baggage sorting system, which directs items of luggage to the right aircraft.

Scientists are accustomed to preparing these kinds of libraries for DNA samples, using standard kits selected according to the cell type and sequencing system in question. But with RNA, although the steps of the process are generally similar, the samples are typically analyzed one-by-one in order to overcome specific difficulties and inherent biases. However, the process developed by Alithea Genomics, called Bulk RNA Barcoding and sequencing (BRB-seq) which was described in a 2021 paper in Genome Biology, enables scientists to quickly and easily prepare and barcode RNA samples for the simultaneous sequencing of up-to 384 samples in a single test tube. In addition to cutting costs and shortening analysis times, Alithea’s process significantly reduces the amount of plastic and chemical compounds required.

Once a sample has been sequenced using conventional machines, the data are run through a proprietary cloud software program that assigns the strands to the correct genome. “Our software is currently available online and it is free-to-access for all BRB-seq users,” says Riccardo Dainese, CEO of Alithea Genomics.
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Industries interested in Fast-tracking research with messenger RNA

BRB-seq was developed by EPFL’s Laboratory of Systems Biology and Genetics (LSBG) to support its own research, after the group was unable to source existing technology that met its needs. The method, which is now being marketed by Alithea, has already been used to successfully analyze adipocyte messenger RNA as part of a study on the expression of mitochondrial genes in fruit flies, with the goal of assessing the efficacy of targeted cancer therapies and gaining new insights into the circadian rhythm. Other research groups, including top pharma companies, have since expressed an interest in the method. “It is very exciting to see that our technology is starting to open doors for the widespread application of RNA sequencing beyond fundamental research and towards industrial applications”, says Dainese.

Because Alithea’s system lets scientists analyze many more samples at a given cost, it paves the way to wider-ranging and more reproducible experiments. More generally, the application of big-data principles to RNA sequencing will be vital to achieving rapid progress in transcriptomics, a field that focuses on the study of the transcriptome – a snapshot of all the messenger RNA in a cell at a given moment in time. Unlike an organism’s genome (i.e., the DNA contained in the nucleus of a cell), which is generally stable and specific to that organism, the transcriptome varies with time, the type of tissue and cell, and various environmental factors. Vast datasets will allow scientists to extract useful statistics and insights into the RNA present under specific circumstances, furthering our understanding of how cells function. Ultimately, such biomarkers could be used to diagnose diseases and develop new drugs.

The CHF 1 million that Alithea raised in May will be used to help market its technology, extend its kit to cover new applications, and customize its analysis software.

See the full article here .

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The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH) is a research institute and university in Lausanne, Switzerland, that specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, and it has three main missions: education, research and technology transfer.

The QS World University Rankings ranks EPFL(CH) 14th in the world across all fields in their 2020/2021 ranking, whereas Times Higher Education World University Rankings ranks EPFL(CH) as the world’s 19th best school for Engineering and Technology in 2020.

EPFL(CH) is located in the French-speaking part of Switzerland; the sister institution in the German-speaking part of Switzerland is The Swiss Federal Institute of Technology ETH Zürich [Eidgenössische Technische Hochschule Zürich] (CH). Associated with several specialized research institutes, the two universities form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles Polytechniques Fédérales] (CH) which is directly dependent on the Federal Department of Economic Affairs, Education and Research. In connection with research and teaching activities, EPFL(CH) operates a nuclear reactor CROCUS; a Tokamak Fusion reactor; a Blue Gene/Q Supercomputer; and P3 bio-hazard facilities.

ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École Polytechnique Fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.

The roots of modern-day EPFL(CH) can be traced back to the foundation of a private school under the name École Spéciale de Lausanne in 1853 at the initiative of Lois Rivier, a graduate of the École Centrale Paris (FR) and John Gay the then professor and rector of the Académie de Lausanne. At its inception it had only 11 students and the offices were located at Rue du Valentin in Lausanne. In 1869, it became the technical department of the public Académie de Lausanne. When the Académie was reorganized and acquired the status of a university in 1890, the technical faculty changed its name to École d’Ingénieurs de l’Université de Lausanne. In 1946, it was renamed the École polytechnique de l’Université de Lausanne (EPUL). In 1969, the EPUL was separated from the rest of the University of Lausanne and became a federal institute under its current name. EPFL(CH), like ETH Zürich (CH), is thus directly controlled by the Swiss federal government. In contrast, all other universities in Switzerland are controlled by their respective cantonal governments. Following the nomination of Patrick Aebischer as president in 2000, EPFL(CH) has started to develop into the field of life sciences. It absorbed the Swiss Institute for Experimental Cancer Research (ISREC) in 2008.

In 1946, there were 360 students. In 1969, EPFL(CH) had 1,400 students and 55 professors. In the past two decades the university has grown rapidly and as of 2012 roughly 14,000 people study or work on campus, about 9,300 of these being Bachelor, Master or PhD students. The environment at modern day EPFL(CH) is highly international with the school attracting students and researchers from all over the world. More than 125 countries are represented on the campus and the university has two official languages, French and English.

Organization

EPFL is organized into eight schools, themselves formed of institutes that group research units (laboratories or chairs) around common themes:

School of Basic Sciences
Institute of Mathematics
Institute of Chemical Sciences and Engineering
Institute of Physics
European Centre of Atomic and Molecular Computations
Bernoulli Center
Biomedical Imaging Research Center
Interdisciplinary Center for Electron Microscopy
MPG-EPFL Centre for Molecular Nanosciences and Technology
Swiss Plasma Center
Laboratory of Astrophysics

School of Engineering

Institute of Electrical Engineering
Institute of Mechanical Engineering
Institute of Materials
Institute of Microengineering
Institute of Bioengineering

School of Architecture, Civil and Environmental Engineering

Institute of Architecture
Civil Engineering Institute
Institute of Urban and Regional Sciences
Environmental Engineering Institute

School of Computer and Communication Sciences

Algorithms & Theoretical Computer Science
Artificial Intelligence & Machine Learning
Computational Biology
Computer Architecture & Integrated Systems
Data Management & Information Retrieval
Graphics & Vision
Human-Computer Interaction
Information & Communication Theory
Networking
Programming Languages & Formal Methods
Security & Cryptography
Signal & Image Processing
Systems

School of Life Sciences

Bachelor-Master Teaching Section in Life Sciences and Technologies
Brain Mind Institute
Institute of Bioengineering
Swiss Institute for Experimental Cancer Research
Global Health Institute
Ten Technology Platforms & Core Facilities (PTECH)
Center for Phenogenomics
NCCR Synaptic Bases of Mental Diseases

College of Management of Technology

Swiss Finance Institute at EPFL
Section of Management of Technology and Entrepreneurship
Institute of Technology and Public Policy
Institute of Management of Technology and Entrepreneurship
Section of Financial Engineering

College of Humanities

Human and social sciences teaching program

EPFL Middle East

Section of Energy Management and Sustainability

In addition to the eight schools there are seven closely related institutions

Swiss Cancer Centre
Center for Biomedical Imaging (CIBM)
Centre for Advanced Modelling Science (CADMOS)
École Cantonale d’art de Lausanne (ECAL)
Campus Biotech
Wyss Center for Bio- and Neuro-engineering
Swiss National Supercomputing Centre