Motor neuron disease (MND) is a progressive neurodegenerative disease leading to muscle weakness, paralysis, and death, on average, 27 months after symptom onset. MND is genetically heterogenous, and heritability evidence suggests that there is a genetic component underlying both inherited and sporadic MND cases. Large-scale genomics provides us with important insights into MND, yet the bioinformatic processing, management and updating of these large datasets can be complex and prohibitive. Our continual development of the MM-BWAP pipeline aims to support the Macquarie University MND Research Centre through streamlining computational analysis and providing additional annotated resources to support interpretation for both researchers and clinicians.
MM-BWAP has been designed in a highly modular fashion using the nextflow workflow language, for both short-read WGS and RNA sequencing data. Carried out in according to clinical best practice, the pipeline also provides detailed quality metrics to ensure high quality outputs. MM-BWAP is structured with a core workflow for alignment, phasing, variant calling, and variant aggregation via genomicsDB, with multiple automated annotated analysis branches dependant on researcher questions: comparative genomics, clinical genomics, genotyping known disease-causing genetic variation (single nucleotide variants, indels, short tandem repeats), polygenic/oligogenic inheritance, dual de novo short tandem repeat identification, and known and cryptic alternative splicing events.
We have utilised an extensive cohort of genomic datasets and sample-matched clinical data, including matched WGS, RNA (blood & brain), pedigrees (where available) and biobank/clinic patient data to identify sequence variation linked to disease, and investigate potential MND biomarkers. Integrating this data with the MM-BWAP pipeline has provided a significant improvement on throughput and quality of the types of analysis we can perform. To facilitate rapid analysis and clinical translation, current (in-progress) extensions to MM-BWAP include generation and integration of interactive reports for comparative genomics (i.e. shared sequence variations, pedigrees, disease loci), and standardised clinical genomics reports.