Cases Studies

Precision Medicine - Biomarkers & Diagnostics

Examples of Services provided by Acobiom

Acobiom provides a wide range of omics services to identify and/or to validate biomarkers as well as in life science research and translational medicine. Some of these services allowed the discovery of new biomarkers, the stratification of patients in clinical trials, the measurement of the safety and tolerability of new compounds, the identification of biomarkers to develop a companion diagnostic, the measurement of the effects of new treatments through RNA-Seq, qRT-PCR, PARE Sequencing experiments…

Case studies of Acobiom’s services

Patient Stratification: Acute Myeloid Leukemia study case

A Pharma company was developing a new chemical drug: a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. Because of the many similarities between human and dog lymphomas, the Pharma company sought to determine the tolerance, efficacy, pharmacokinetics/pharmacodynamics (PK/PD) relationships of this new chemical drug in lymphoma, and potential biomarkers that could be translated into human trials. This new chemical drug was tested in a phase I/II clinical trial in acute myeloid leukemia. As part of this project, Acobiom was appointed to investigate this potential of this new chemical drug in a phase III clinical trial and a new clinical indication. The Acobiom’s outcomes and recommendations allowed to stratify a subset of patients (good responders).

Safety/Toxicity profiling and Patient Stratification

A Biotech company was investigating the safety and antiviral effects of a new anti-HIV compound with a unique mechanism of viral replication inhibition. This clinical trial was a randomized, double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV-infected patients. The primary objective of this study was to assess the safety and tolerability of this new anti-HIV compound after repeated oral administrations in subjects infected by HIV. As part of this project, the Biotech company qualified circulating (blood) miRNA biomarkers of treatment according to the criteria of safety and toxicity. Acobiom supported this Biotech company in its phase III study technically (providing qRT-PCR analyses) and according to the guidelines of Health Authorities.

Target discovery/Identification: Breast cancer study case

In collaboration with a scientific team involved in Down Syndrome (DS), Acobiom investigated new targets in breast cancer. Indeed, the patterns of malignancies in DS are unique and highlight the relationship between chromosome 21 and breast cancer. Only 2 women (0.7%) with DS had a diagnosis of breast cancer (Chicoine B et al., 2015 Intellect Dev Disabl). Blood samples from 2 groups of patients (group A: female patients without breast cancer but presenting a Down syndrome; group B: female patients with breast cancer and presenting a DS) were analyzed through RNA-Seq approach. In parallel, RNA-Seq libraries have been performed on tumoral tissues from female patients suffering from breast cancer but without Down syndrome. Acobiom’s approach allows the identification of specific signaling pathways in cancer and immunity, with specific key genes.

Companion Diagnostic: Pancreatic cancer study case

During a clinical trial phase III and from a whole blood collection, Acobiom identified different sets of RNA biomarkers associated with the different sub-populations of patients (responders/non responders). These blood RNA biomarkers were discovered with no a priori and thanks to the proprietary genomic platform of the company (combination of NGS, bioinformatics and biostatistics tools to analyze Big Data). Then, using Real-Time PCR, candidate genes were selected for test significance and a Gene Expression-based Score was established.

Measuring the effects of a new treatment (safety: A translational bridge between mouse models and human)

A company was developing a new treatment and needed to measure its effects by comparing the expression of targeted genes on different mouse groups. The objective was to design and measure the gene expression levels of these targeted genes via a reliable, standardized and transferable Real-Time PCR-based protocol under clinical guidelines. Several replicates were performed. The analyses included: the identification and the selection of housekeeping genes, the RNA extraction from samples, the primer design, the qRT-PCR experiences and the statistical analysis of generated data.

Measuring the treatment effects in vegetal: Rice (Oryzae sativa) and PARE sequencing (Degradome)

It has been known that many microRNAs (miRNAs) are involved in the regulation for plant development and defense mechanism by regulating the expression of certain genes. An international academic group developed a new treatment for Rice (Oryzae sativa) and revealed during a time-course miRNA cleavage sites and their target genes in response to infection. The objective was to design and map degrading RNA using a specific Next Generation Sequencing protocol, the PARE sequencing (Degradome) that provides information about uncapped transcripts that undergo degradation.

Gene expression analysis of a bacterial strain in several conditions (RNA-Seq analysis / Biomarker identification)

An academic laboratory ran a RNA-Seq experiment on a bacterial strain in several conditions and searched to analyze the obtained RNA-Seq data. From the sequence raw files and the study description, Acobiom performed the analysis of these RNA-Seq data (cleaning, mapping on reference and counting gene expression level). As all the genes identified as statistically differentially expressed between the distinct conditions could be potential biomarkers, Acobiom performed several differential expression analyses, crossed the results on different methods in order to reinforce the results, and annotated them with biological reference data.
To sum-up, the academic laboratory was assisted in treating and analyzing all the RNA-Seq data and in specifying criteria to select biomarkers.

Why dealing with Acobiom ?

Acobiom developed, validated and brought into clinical practice biomarkers and diagnostics based on its state-of-art experience and technologies.

Dealing and partnering with Acobiom brings full advantages for its partners as:

– A unique Proprietary Biomarker Platform including multivariate Genotype/Phenotype resources,
– Over 20 years’ experience in customized analyses to identify and validate RNA/DNA biomarkers from tissues and liquid biopsies,
– A scientific and process workflow approved/validated by clinical practice,
– Cutting-edge bioinformatics and data science tools,
– Liquid biopsy based methods and processes,
– Top down strategy for biomarker identification,
– No prior information required to identify new biomarkers,
– Large panel of health applications (cancer, infection, hematology, neurology, inflammation…),
– Patents on prognostic biomarkers/predictive biomolecular signature,
– 60 scientific publications related to biomarkers, diagnostics and precision medicine.

A Research Tax Relief

Acobiom has been granted a Research Tax Relief (« Crédit Impôt Recherche ») until 2019 by the French Ministry of Research and Technology, enabling its industry clients to apply the company’s services to their research tax credits.