Vertex labels swapping Edges swapping

Vertex labels swapping Edges swapping Vertex labels swapping Edges swapping - Start

Added : 2018-03-18 Views :43K

Download Presentation

Vertex labels swapping Edges swapping




Download Presentation - The PPT/PDF document "Vertex labels swapping Edges swapping" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.



Presentations text content in Vertex labels swapping Edges swapping

Slide1

Vertex labels swappingEdges swapping Pathway activity levels with ratio

Abstract

Metabolic pathway activity estimation from RNA-Seq data

Yvette Temate-Tiagueu, Qiong Cheng, Meril Mathew, Igor Mandric, Olga Glebova, Nicole Beth Lopanik, Ion Mandoiu and Alex Zelikovsky

Department of Computer Science, Department of Biology, Georgia State UniversityComputer Science and Engineering, University of Connecticut

Our Contribution

Using Kegg: database resource for understanding high-level functions and utilities of the biological system from molecular-level information. [Kanehisa M., and Goto S., 2000]A novel graph-based approach to analyze pathways significance Representing a pathway as a set an inferring activity from the information extracted from those setsValidating the two approaches through differential expression analysis at the transcripts and genes level and also through qPCR experiment

Objectives

Methods

Results

1

. Moran NA:

Symbiosis. Curr Biol 2006, 16:R866–R871. 2. McFall-Ngai M, Hadfield MG, Bosch TCG, Carey HV, Domazet-Loso T, Douglas AE, Dubilier N, Eberl G, Fukami T, Gilbert SF et al: Animals in a bacterial world, a new imperative for the life sciences. Proc Natl Acad Sci USA 2013, 110(9):3229-3236. 3. Haine ER: Symbiont-mediated protection. Proc R Soc B-Biol Sci 2008, 275(1633):353-361. 4. Lopanik NB: Chemical defensive symbioses in the marine environment. Funct Ecol 2013, 28:328-340. 5. Cragg GM, Newman DJ: Natural products: A continuing source of novel drug leads. Biochimica Et Biophysica Acta-General Subjects 2013, 1830(6):3670-3695. 6. Piel J: Metabolites from symbiotic bacteria. Natural Product Reports 2009, 26(3):338-362. 7. Gerwick WH, Moore BS: Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem Biol 2012, 19(1):85-98.

Our experimental studies on Bugula neritina RNA-seq data (mutualistic symbiosis data vs none) show that, by analyzing metabolic pathways using our tool XPathway, we can effectively locate pathways which activities level significantly differ. This result is been validated through qPCR.This project is supported in part by the Molecular Basis of Disease fellowship of GSU

Conclusions and Future Work

The application of RNA-Seq has allowed various differential analysis studies including differential expression for pathways. A standard approach to study the metabolic differences between species is metabolic pathway. In this study, we introduce a novel approach to characterize pathways activity levels of two samples. We present XPathway, a set of pathways activity analysis tools based on Kegg-Kaas mapping of proteins to pathways. We applied our proposed methods on RNA-Seq Bugula neritina metagenomics data. We successfully identified several pathways with differential activity levels using our novel computational approaches implemented in XPathway. Further validation of initial results is conducted through qPCR.

Develop efficient algorithms for reliable estimation of pathway activity level Identify pathways which activities significantly differ between two conditions

Validation

Experimental studies

: Bugula neritina

In United States - Three sibling species:

Deep-water (West coast of United States) Shallow-water (West and Southern East coasts) Northern Atlantic (Northern East coast)Illumina sequence paired-end reads:Sample 1: Bugula with symbiont Sample 2: Bugula without symbiont

50bp paired-end reads

200bp mean fragment lengthAssembly into contigs by Trinity BLAST with Swissprot database

Sample 1

Sample 2

Topology-based estimation of pathway

significance

EM-based

estimation of pathway activity

Selected

pathways for

qPCR

validationqPCR

Model 1: permutation of labels

a

e

b

c

c

a

d

e

b

d

Model 2: permutation of edges

a

c

b

c

d

a

b

d

RNA-

seq

reads

2 Samples

Trinity

Binary EM

Contigs

IsoDE

Contigs

validation

KEGG,

SEED

Ortholog

groups

K00161

K00162

K00163

KEGG,

SEED

Ortholog

groups

K00161

K00162

K00163

Graph-based

Pathway significance

Pathway activity

Differentially expressed

pathways

Experimental validation

Proteins

MAFSAED

VLK EYD

RRMEAL

BLAST

b

inary activity status of w

 

 

activity level of pathway w

 

 

 

 

 

 

 

Bootstrapping:

Repeat

1000

times

 Randomly switch edges

 Compute density of the largest component

Sort

wrt

to density

Find the rank of the observed induced subgraph

    

For

gene expression analyses:

Select pathways with significantly different activity

Select DE transcripts from these pathways

Select the genes from these transcripts

Primers are created to test genes per condition

Preliminary results

More primers ordered

References

In induced

graph:

#

nodes N

#

edges M

#

green connected components

#

0 in- & out-degrees

Density

of the induced graph:

M/(N-1)


About DocSlides
DocSlides allows users to easily upload and share presentations, PDF documents, and images.Share your documents with the world , watch,share and upload any time you want. How can you benefit from using DocSlides? DocSlides consists documents from individuals and organizations on topics ranging from technology and business to travel, health, and education. Find and search for what interests you, and learn from people and more. You can also download DocSlides to read or reference later.
Youtube