Case Studies

Precision Medicine - Biomarkers & Diagnostics

Examples of scientific collaborations using Acobiom’s expertise

The scientific and technical expertise of Acobiom has been demonstrated in a wide range of studies to identify and/or to validate biomarkers as well as in several researches in translational medicine and life science. Some of these studies have led to 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 companion diagnostics, the measurement of the effects of new treatments by RNA-Seq, qRT-PCR, PARE Sequencing experiments…

Acobiom: its technical and scientific expertise in few examples

Patient Stratification in Acute Myeloid Leukemia

A pharmaceutical company developed a new chemical drug: a topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. This Pharma company sought to determine the tolerance, the efficacy,  the 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 has been 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 in 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 in Breast cancer

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 been diagnosed with a 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 in Pancreatic cancer

During a clinical trial phase III of a new therapy in pancreatic cancer, Acobiom identified several sets of blood RNA biomarkers (total blood) 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 technical platform of the company (combination of NGS, bioinformatics and biostatistics tools to analyze Big Data). Then, using Real-Time PCR, candidate genes were selected to the development of a future companion diagnostic test.

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.

Gene expression analysis of a bacterial strain in several conditions (RNA-Seq analyses / 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 genome and counting gene expression level). As all the genes identified could be potential biomarkers (they were statistically differentially expressed in the distinct studied conditions), Acobiom performed several differential expression analyses, crossed the obtained data using different methods, and annotated the results 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.

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

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

Acobiom: its technical and scientific expertise in few key-points

Collaborating with Acobiom brings to the partners of the company to benefit from many advantages:

– A unique platform to identify biomarkers including multivariate resources of Genotypes and Phenotypes,
– Over 20 years’ experiences in performing customized analyses to identify and validate RNA / DNA biomarkers from tissues and liquid biopsies,
– An analysis protocol that doesn’t require a priori information to identify new biomarkers,
– Specific methods and processes to analyze liquid biopsies,
– A scientific and process workflow approved/validated by clinical practice,
– Cutting-edge bioinformatics and data science tools,
– A large panel of health applications (cancer, infection, hematology, neurology, inflammation…),
– An expertise illustrated in 60 scientific publications related to biomarkers, diagnostics and precision medicine, in several patents on prognostic biomarkers and predictive biomolecular signatures,

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