Bayesian Decomposition Michael Ochs Fox Chase Cancer Center - - PowerPoint PPT Presentation

▶
bayesian decomposition
SMART_READER_LITE
LIVE PREVIEW

Bayesian Decomposition Michael Ochs Fox Chase Cancer Center - - PowerPoint PPT Presentation

Apr 16, 2023 384 likes •681 views

Bayesian Decomposition Michael Ochs Fox Chase Cancer Center Bioinformatics Fox Chase Cancer Center Making Proteins Bioinformatics Fox Chase Cancer Center A Closer Look at Translation Post-Trans- lational Modification RNA Splicing miRNA

slide-1
SLIDE 1

Bioinformatics Fox Chase Cancer Center

Bayesian Decomposition

Michael Ochs Fox Chase Cancer Center

slide-2
SLIDE 2

Bioinformatics Fox Chase Cancer Center

Making Proteins

slide-3
SLIDE 3

Bioinformatics Fox Chase Cancer Center

A Closer Look at Translation

RNA Splicing miRNA Post-Trans- lational Modification

slide-4
SLIDE 4

Bioinformatics Fox Chase Cancer Center

Identifying Pathways

www.promega.com

A B C D

A B C D 1 2 3

slide-5
SLIDE 5

Bioinformatics Fox Chase Cancer Center

Goal of Analysis

Take measurements of thousands of genes, some of which are responding to stimuli

  • f interest

* * 1 2 3 * * * * then identify the pathways And find the correct set of basis vectors that link to pathways

slide-6
SLIDE 6

Bioinformatics Fox Chase Cancer Center

BD: Matrix Decomposition

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

Data X

gene 1 gene N * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * gene 1 gene N pattern 1 pattern k condition 1 condition M * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * pattern 1 pattern k condition 1 condition M

Distribution of Patterns Patterns of Behavior =

The behavior of

  • ne gene can be

explained as a mixture of patterns with different behaviors

slide-7
SLIDE 7

Bioinformatics Fox Chase Cancer Center

Patterns as Basis Vectors

slide-8
SLIDE 8

Bioinformatics Fox Chase Cancer Center

BD with Knowledge of Classes

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

Data X

gene 1 gene N * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * gene 1 gene N pattern 1 pattern k condition 1 condition M * * * * 0 0 0 0 0 0 0 0 0 0 * * * * 0 0 0 0 0 0 0 0 0 0 * * * * * * * * * * * * pattern 1 pattern k condition 1 condition M

Distribution of Patterns Patterns of Behavior =

slide-9
SLIDE 9

Bioinformatics Fox Chase Cancer Center

BD Structure

Atomic Domains Allow Encoding

  • f Biological Information

Markov Chain Monte Carlo is used to explore possible sets of distributions and patterns

slide-10
SLIDE 10

Bioinformatics Fox Chase Cancer Center

Project Normal Data

  • Download Data from CAMDA Site
  • Adjust for Background Measurement
  • Take Ratios
  • Calc Mean and SDOM for Each Ratio
  • Eliminate M3T and M4T Data
  • Eliminate 24 Points with Only 1 Data Pt

– 99% 4 Pts, 1% 3 Pts, 0.1% 2 Pts

slide-11
SLIDE 11

Bioinformatics Fox Chase Cancer Center

Filtering of Genes

  • Eliminated all ESTs

– Annotated Remaining Genes from Gene Ontology on Unigene Name

  • Annotated all Genes on Clone ID

– 24% Changed Unigene Cluster – 948 Clones Had GO Process Information

slide-12
SLIDE 12

Bioinformatics Fox Chase Cancer Center

Updating Annotations: ASAP

http://bioinformatics.fccc.edu/

slide-13
SLIDE 13

Bioinformatics Fox Chase Cancer Center

Bayesian Decomposition

  • Encoded 3 Known Patterns

– Kidney, 6 Conditions – Liver, 6 Conditions – Testis, 4 Conditions

  • Allowed 1 - 3 Additional Patterns

– Account for Behavior Unrelated to Tissue Specific Expression

slide-14
SLIDE 14

Bioinformatics Fox Chase Cancer Center

Fitting the Data

slide-15
SLIDE 15

Bioinformatics Fox Chase Cancer Center

Four Patterns

0.05 0.1 0.15 0.2 0.25 0.3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Kidney Liver Testis Background

slide-16
SLIDE 16

Bioinformatics Fox Chase Cancer Center

Five Patterns

0.05 0.1 0.15 0.2 0.25 0.3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Kidney Liver Testis Background 1 Background 2

slide-17
SLIDE 17

Bioinformatics Fox Chase Cancer Center

Four vs Five Patterns

slide-18
SLIDE 18

Bioinformatics Fox Chase Cancer Center

Gene Ontology

  • Identify Genes “Only” in One Pattern

– See if Pattern Enhanced in GO

  • Identify Genes in a Pattern

– 3σ above Zero in Distribution – Look at GO Assignments

  • Identify Genes Lacking in Pattern

– Eliminate Background (Genes > 70%) – Look for Genes Not in Pattern (3σ)

slide-19
SLIDE 19

Bioinformatics Fox Chase Cancer Center

Genes Only in Kidney by GO

endocytosis * neuropeptide signaling pathway anion transport * inorganic anion transport * vitamin B12 transport vitamin/cofactor transport * transmembrane receptor protein tyrosine kinase signaling pathway * enzyme linked receptor protein signaling pathway * receptor mediated endocytosis chloride transport * neurotransmitter transport *

Sodium transport, vesicle- mediated transport, amino acid transport, folate transport, homophilic cell adhesion, cell-cell adhesion, monovalent inorganic cation transport metal ion transport

From Old Annotations

> 10x Enhancement

slide-20
SLIDE 20

Bioinformatics Fox Chase Cancer Center

Genes Only in Liver by GO

small molecule transport, histogenesis and

  • rganogenesis,

embryogenesis and morphogenesis, lipid metabolism

protein targeting response to pest/pathogen/parasite response to chemical substance response to abiotic stimulus homophilic cell adhesion * cell-cell adhesion * drug susceptibility/resistance * response to drug cellular defense response antigen processing, endogenous antigen via MHC class I" antigen processing

From Old Annotations

> 10x Enhancement

slide-21
SLIDE 21

Bioinformatics Fox Chase Cancer Center

Genes Only in Testis by GO

nuclear organization and biogenesis, chromosome

  • rganization and

biogenesis, cell

  • rganization and

biosynthesis

development * microtubule-based process microtubule-based movement regulation of transcription from Pol II promoter spermatogenesis * gametogenesis * reproduction * meiotic recombination DNA recombination

From Old Annotations

> 10x Enhancement

slide-22
SLIDE 22

Bioinformatics Fox Chase Cancer Center

Kidney Genes, 3σ , > 2 fold

G-protein coupled receptor protein signaling pathway endocytosis S phase of mitotic cell cycle homophilic cell adhesion cell-cell adhesion perception of light perception of abiotic stimulus nitrogen metabolism anion transport amine metabolism mitotic cell cycle inflammatory response amino acid metabolism

slide-23
SLIDE 23

Bioinformatics Fox Chase Cancer Center

Testis Genes, 3σ, >4 fold

S phase of mitotic cell cycle protein folding microtubule-based movement mitotic cell cycle regulation of cell shape and cell size spermatogenesis gametogenesis reproduction

slide-24
SLIDE 24

Bioinformatics Fox Chase Cancer Center

Liver Genes, 3σ, >3 fold

tricarboxylic acid cycle

  • rganogenesis

morphogenesis sensory perception response to chemical substance response to abiotic stimulus catabolic carbohydrate metabolism main pathways of carbohydrate metabolism energy derivation by oxidation of organic compounds energy pathways drug susceptibility/resistance response to drug amino acid metabolism

slide-25
SLIDE 25

Bioinformatics Fox Chase Cancer Center

Genes Absent in Patterns

microtubule-based process spermatogenesis gametogenesis reproduction

  • bsolete

biological_process unknown regulation of cell shape and cell size regulation of transcription from Pol II promoter monosaccharide metabolism

Absent in Kidney

microtubule-based movement actin cytoskeleton

  • rganization and biogenesis

actin filament-based process cell differentiation spermatogenesis gametogenesis reproduction

Absent in Liver

slide-26
SLIDE 26

Bioinformatics Fox Chase Cancer Center

Genes Absent in Background 1

mitotic cell cycle spermatogenesis gametogenesis reproduction regulation of transcription from Pol II promoter endocytosis actin cytoskeleton organization and biogenesis actin filament-based process protein targeting protein modification

  • bsolete

biological_process unknown

slide-27
SLIDE 27

Bioinformatics Fox Chase Cancer Center

Genes Present in Two Tissues

perception of light perception of abiotic stimulus amine metabolism amino acid metabolism immune response defense response homophilic cell adhesion cell-cell adhesion

Kidney/Testis not Liver

mitotic cell cycle

Kidney/Liver not Testis

slide-28
SLIDE 28

Bioinformatics Fox Chase Cancer Center

Acknowledgements

  • This Work

– Tom Moloshok – DJ Datta (Cambridge) – Andrew Kossenkov – Bill Speier (JHU)

  • Colleagues

– J. Robert Beck – Frank Manion

  • Programming

– Jeffrey Grant – Elizabeth Goralczyk – Luke Somers

  • Others

– G. Parmigiani (JHU) – T. Brown (Columbia) – E. Korotkov (RAS)