SErvices for pharma

From Discovery to CDx

BioClavis can help you each step along the way of drug discovery & development

Discovery

With the advent of next generation sequencing, the cost for sequencing has drastically reduced over the past decades, yet the practicality to run large projects remains limited. This makes high-throughput research in target ID, selection, and validation as well as mode of action and pre-clinical studies with transcriptomic endpoints costly and often unfeasible.

Maximise sequencing throughput

BioClavis circumvents these issues by leveraging the highly efficient TempO-Seq® transcriptomic/genomic platform developed by BioSpyder. TempO-Seq is specifically designed for very efficient profiling of molecular signatures or whole transcriptomes and is therefore ideal for high-throughput transcriptomic studies. Using a targeted approach with next generation sequencing readout, TempO-Seq maximises the sequencing throughput and allows for indexed pooling of up to 6,144 samples per sequencing run.

We can work with you to incorporate high-throughput transcriptomics in your in vitro or in vivo discovery system.

Targeted but not limited

TempO-Seq is a highly flexible assay, both in terms of gene multiplexing (custom panels ranging from tens to thousands of genes up to whole transcriptome) and input (crude cell lysates, whole blood, FFPE tissue, or purified RNA/DNA). Currently, we offer whole transcriptome panels for human, rat, and mouse. We also offer S1500(+) surrogate panels, specifically designed for economical transcriptome-wide pathway-based high-throughput transcriptomics (HTTr), for human, rat, mouse, and zebrafish. Custom panels can be designed for any species of interest, for any number of genes, or variants and isoforms.

Below is a non-exhaustive list of projects TempO-Seq enables:

To find out more, please contact us.

TempO-Seq enables a variety of early clinical development activities. Below is a non-exhaustive list of potential activities BioClavis can support:

Late clinical development (PHASE III) & Post-Approval

TempO-Seq features render it particularly suitable for profiling and stratifying large cohorts of patients from commonly used clinical sample types, such as biopsies, FFPE tissue, whole blood, or plasma. TempO-Seq allows for efficient analysis of large sample numbers with fully customisable biomarker panels of tens to thousands of genes (up to the whole transcriptome).

Unlike many other technologies, TempO-Seq offers unlimited gene multiplexing. Therefore, biomarker panels for patient stratification can include as many genes and variants as are necessary. Extra genes can be added on at virtually no extra cost. Importantly, the TempO-Seq assay does not require any proprietary instrumentation, runs in a simple 96- or 384-well plate format in < 6 h (with less than an hour hands-on time), and can therefore be easily implemented in a real-world clinical setting.

Therefore, TempO-Seq is ideally suited for development of Companion Diagnostics (CDx).

Regardless of whether you would like to implement known signatures with a TempO-Seq assay or develop a new signature based on TempO-Seq data, please feel free to contact us. Our team is happy to support CDx development activities.

Assay capabilities & Specifications

Below is a list of assay capabilites and specifications.
For more background, please visit our resources page.

Our off-the-shelf panels include:

• whole transcriptome

  • human, mouse, and rat

• Surrogate transcriptome

  • human, mouse, rat, and zebrafish

  • bioinformatically designed to include 70-80% of pathways covered by the whole transcriptome with only ~4000 probes (maximally diverse expression and minimal co-regulation)

  • particularly useful for large pathway-level screens of biological activity

We can create new, fully customised panels for you, either as subsets of already existing panels, or by designing new probes. This can be include any isoform, mutation (SNP or fusion gene) and species, as long as you are able to provide a reference transcriptome/genome or reliable FASTQ files.

TempO-Seq runs directly from tissue or cell lysates without RNA extraction, purification, or cDNA synthesis. This drastically increases sensitivity, as RNA extraction can cause loss of RNA or introduce size bias. The assay is based on hybridisation of specific probes to the sample’s RNA in situ, which is a highly efficient and conserved molecular process. Only minute amounts of sample are needed for a successful assay run.

Example types of input:

• Crude cell lysates in a 96- or 384-well format

• 2-10 mm^2 of a 4 micron FFpe section

  • can be H&E or antibody stained, as long as reagents are nuclease-free

  • can also be smaller (e.g. LCM), please speak to us.

• sorted fixed cells (ICS-FACS)

• Laser-capture microdissected (LCM) samples from ffpe tissue

• whole blood

• whole zebrafish embryo lysate

TempO-Seq has provided good results from many “difficult” or “low input” samples that are difficult to profile with other established technologies. Our sample requirements can be found here, but please feel free to speak to us if you are unsure about your sample type or would like to know more.

As the assay circumvents the steps of RNA extraction/purification (which can result in significant RNA loss), reverse transcription (which is carried out by an enzyme that is evolutionarily designed to introduce errors), and does not require pre-amplification (which can induce bias), TempO-Seq offers excellent accuracy.

Based on highly efficient and sensitive hybridisation of specific probes to regions of interest within a gene, the assay is capable of detecting a lower threshold of ~ 16 molecules and offers high reproducibility down to 10 pg of RNA input (single cell equivalent).

Read TempO-Seq publications here.

Based on the assay biochemistry, TempO-Seq enables high sample multiplexing on the sequencer - enabling the screening of large patient cohorts quickly and inexpensively.

Get in touch

If you are interested in our tempo-seq services for drug discovery, development, or companion diagnostics, Please complete the form below and a member of our team will be back in touch shortly.