Bioinformatics Methods for Pathogen Bioinformatics Methods for - - PowerPoint PPT Presentation

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Bioinformatics Methods for Pathogen Bioinformatics Methods for - - PowerPoint PPT Presentation

Dec 05, 2022 181 likes •391 views

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:

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Bioinformatics Methods for Pathogen Identification Bioinformatics Methods for Pathogen Identification

  • W. Evan Johnson, Ph.D.

Divsion of Computational Biomedicine, BUSM Department of Biostatistics, BUSPH Bioinformatics Program, BU Email: wej@bu.edu Twitter: @wejlab

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The History of the Microbiome The History of the Microbiome

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Whole Metagenome Sequencing and Pathogen Detection Whole Metagenome Sequencing and Pathogen Detection

  • Existing diagnostics:

Culture, PCR, etc.

  • Metagenomic sequencing

Existing analytic methods include: Marker genes Taxonomy mapping Assembly

  • Can we do better?
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PathoScope:

`Plug and Play' Metagenomic Framework

PathoScope:

`Plug and Play' Metagenomic Framework

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RNA Sequencing

Pneumonia Influenza

Host Response Pathways Collect specimen Genome Library

Influenza Pneumonia RSV

  • E. coli

Anthrax HIV Plague

PathoScope Analysis

(Genome Research, 2013)

Influenza Pneumonia RSV

Align to Microbial Genomes Bayesian Mixture Modeling Microbial Abundance Align to Human Genome

Human

Sparse Baysian Factor Analysis Immune Pathway Activity

ASSIGN Profiling

(Bioinformatics, 2015)

Human

Pathway Activation Pathogen Abundance Control Asthma

Microbiome and Host Response in Asthma

(BMC Med Genomics, 2015)

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PathoScope:

`Plug and Play' Metagenomic Framework

PathoScope:

`Plug and Play' Metagenomic Framework

  • PathoScope Core Modules:

 PathoLib: Automatic genome library extraction and

  • ptimization

 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

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animalcules (Bioconductor) animalcules (Bioconductor)

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Aperiomics Aperiomics

Pleural Effusion:

  • F. nucleatum

Metagenome sequencing to solve hard-to-diagnose infections

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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!
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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?
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Acknowledgements Acknowledgements

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