Bioinformatics Methods for Pathogen Bioinformatics Methods for - PowerPoint PPT Presentation

Bioinformatics Methods for Pathogen Bioinformatics Methods for Pathogen Identification Identification W. Evan Johnson, Ph.D. Divsion of Computational Biomedicine, BUSM Department of Biostatistics, BUSPH Bioinformatics Program, BU Email: wej@bu.edu Twitter: @wejlab

The History of the Microbiome The History of the Microbiome

Whole Metagenome Sequencing and Pathogen Whole Metagenome Sequencing and Pathogen Detection Detection  Existing diagnostics:  Culture, PCR, etc.  Metagenomic sequencing  Existing analytic methods include:  Marker genes  Taxonomy mapping  Assembly  Can we do better?

PathoScope: PathoScope: `Plug and Play' Metagenomic Framework `Plug and Play' Metagenomic Framework

Collect specimen Host Response Pathways RNA Sequencing Influenza Pneumonia Genome Library Influenza E. coli ASSIGN Profiling PathoScope Analysis Plague RSV Pneumonia (Bioinformatics, 2015) (Genome Research, 2013) Human HIV Anthrax Align to Human Genome Align to Microbial Genomes Pathway Activation Pneumonia RSV Influenza Human Sparse Baysian Factor Analysis Bayesian Mixture Modeling Pathogen Abundance Microbial Abundance Immune Pathway Activity Control Asthma Microbiome and Host Response in Asthma (BMC Med Genomics, 2015)

PathoScope: PathoScope: `Plug and Play' Metagenomic Framework `Plug and Play' Metagenomic Framework  PathoScope Core Modules:  PathoLib: Automatic genome library extraction and optimization  PathoMap: Align reads and filter reads from host, etc.  PathoID: Reassign ambiguous reads, identify strains present, and estimate proportions of RNA/DNA  PathoReport: Summary reports, XML report, contigs, annotations etc  PathoScope Optional Modules:  PathoQC: Parallel quality control wrapper for multiple QC programs.  PathoDB: Extract annotation from NCBI (name, genes, products,lineage, etc) Hong et al., Microbiome , 2015

animalcules (Bioconductor) animalcules (Bioconductor)

Aperiomics Aperiomics Metagenome sequencing to solve hard-to-diagnose infections Pleural Effusion: F. nucleatum

Recent Aperiomics Case Study Recent Aperiomics Case Study  68 year old woman from West Virginia  Unexplained pain much of her adult life  Diagnoses: chronic Lyme, arthritis, pain unknown origin  Blood test, metagenomic profiling  30M DNA seqs, 270 matched Mtb  Not Lyme, she had extrapulmonary TB!

Future Efforts Future Efforts  Further Software and Tool Development:  R toolkit and visualization—Animalcules package!  Longitudinal analysis  Applications  Cancer: lung, pancreatic, colon cancer, head & neck Efficacy of Immunotherapies  Infectious disease: tuberculosis (extrapulmonary, pediatric), HIV, other pulmonary infections, etc  Incubation of these projects at BU?

Acknowledgements Acknowledgements Metagenomics Methods Keith Crandall (GWU) Changjin Hong Crystal Icenhour (CEO) Mani Solaiappan Yuan (Alvin) Chen (CSO) Yue (Jason) Zhao Ying Shen Keith Crandall (GWU) Eduardo Castro-Nallar (GWU) Aperiomics