Bioinformatics

Almac Diagnostic Services Bioinformatics Team offer a high quality service for analysis of genomics data across a range of platforms (including Next Generation Sequencing (NGS), Nanostring and qPCR) and biomaterials, underpinned by our extensive experience analysing data from both in-house development projects and commercial clinical projects. We have access to the latest Illumina DRAGEN Secondary Analysis pipelines hosted on the Illumina Connected Analytics (ICA) cloud platform allowing robust, flexible end-to-end data solutions at scale from quality control (QC), processing and interpretation to data transfer directly to the client.

The team offers the following capabilities across the core platforms listed below, however much of our work is tailored to specific data challenges for clients, which typically require bespoke solutions.

Technology analysis pipelines

RNA

NGS (Next Generation Sequencing)

• Almac established QC & pre-processing steps for bulk (Illumina TruSeq™ RNA Exome, Total RNA-Seq and mRNA Stranded), small and single-cell RNA-Seq.
• Bulk RNASeq analysis includes access to the Clara^T Total mRNA Report.
• Custom workflow development tailored to answer specific customer questions

Nanostring

• nSolver QC and data normalisation
• Includes access to IO360/BC360 Data Analysis Reporting if applicable.

qPCR

• In-house software for reproducible data QC & pre-processing

DNA

Whole Exome Sequencing (WES) / Whole Genome Sequencing (WGS)

• Illumina DRAGEN QC and secondary analysis for WES (Whole Exome Sequencing) or WGS (Whole Genome Sequencing)
• Custom annotation, filtering and interpretation options available

Whole Genome Methylation Sequencing (WGMS)

• Almac established QC and processing steps for EM-seq – WGMS (Whole Genome Methylation Sequencing)
• DRAGEN pipelines for bisulphite-seq and custom workflow development tailored to answer specific customer questions

Medium / Small Variant Panels

• Illumina DRAGEN Analysis Software for small variant, CNV and fusion detection from Illumina TruSight™ Oncology 500 (TSO500) tissue and ctDNA panels.
• Archer Analysis pipelines applied to Archer® FusionPlex, VariantPlex and LiquidPlex panels
• Personal Genome Diagnostics (PGDx) analysis pipelines applied to PGDx elio tissue and plasma panels.
• Almac can also develop custom pipelines for other targeted panels

To see our range or panel solutions visit Platforms & Technologies

Bioinformatics for the biomarker discovery process

Almac Diagnostic Services has a well-developed gene expression biomarker discovery process incorporating in-house software that has been established over many years. Our pipelines are applicable to expression platforms, such as RNA-Seq, and Nanostring.

Our expertise in biomarker development has been demonstrated through our own research in the oncology field, where we have discovered and validated a number of Almac proprietary biomarkers from FFPE studies including DDIR, Angio, EMT, ProstateDx and ColDx signature.

We also have extensive expertise in the non-oncology field supporting client biomarker development projects in Chronic Disease. These studies typically use fresh samples rather than archival samples, meaning degradation is less of an issue; however clinical endpoints are often poorly defined. In these cases we can perform analysis to guide selection of the most appropriate endpoint for your study.

Our Bioinformatics team can perform post-hoc analyses to tailor developed models to specific patient subgroups, incorporation of other data types such as pharmacokinetic (PK Biomarkers), and building multi factorial models including predictive clinical factors in addition to off the shelf best practice solutions for differential expression and pathway / functional enrichment analyses.

Almac Diagnostic Services can offer clients the following proprietary Bioinformatics analysis solutions to facilitate their Biomarker Discovery process:

• Quality Control (QC) & Exploratory Analysis (EA)
• Subtyping Workflow
• Signature Generation Workflow

Quality Control (QC) & Exploratory Analysis (EA)

For optimal biomarker discovery, Almac’s QC and EA process ensures the best starting point for signature generation. We have defined QC processes and thresholds for most expression data generating platforms such as RNA-Seq and microarray. Our EA tool works with any expression data type and provides insight into all relationships within, and between, technical and clinical variables and the data structure based on principal components. The EA process aims to identify key factors driving sample groups within the dataset and reduce or remove the impact of technical effects that may hinder the biomarker discovery process.

Subtyping workflow

Almac’s unsupervised analysis process is designed to find the underlying biological structure driving sample separation within a dataset, to identify stable sample and gene clusters driven by these transcripts. This process is of particular benefit when the response endpoint is poorly defined. Transcripts are identified by an iterative process of removing noise and testing the stability of resulting clusters. Once robust sample and gene clusters are identified, the association of sample characteristics to these clusters is tested, and functional enrichment of the gene clusters is performed to characterise the biology of the subgroups.

Signature Generation Workflow (SGW)

Almac’s SGW has been developed according to MAQC best practice. All feature selection and performance metric generation are performed under a robust cross-validation process. The machine learning method depends on the nature of the endpoint of interest and dichotomous classifiers or continuous predictors can be developed to binary or continuous measures of response. Almac has custom-built functions to visualise the biological relevance of resulting signatures to guide final model selection, along with appropriate measures of performance.