Putting genetic interactions in context through a global modular decomposition
This presentation is the property of its rightful owner.
Sponsored Links
1 / 23

Putting genetic interactions in context through a global modular decomposition PowerPoint PPT Presentation


  • 54 Views
  • Uploaded on
  • Presentation posted in: General

Putting genetic interactions in context through a global modular decomposition . Jamal. Motivation. Genetic interaction  provide powerful perspective how gene functions specific mechanisms that give rise to these interactions not well understood

Download Presentation

Putting genetic interactions in context through a global modular decomposition

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Putting genetic interactions in context through a global modular decomposition

Putting genetic interactions in context through a globalmodular decomposition

Jamal


Putting genetic interactions in context through a global modular decomposition

Motivation

  • Genetic interaction provide powerful perspective how gene functions

  • specific mechanisms that give rise to these interactions not well understood

  • Requires a thorough study of genetic interaction networks  understand the structure of the network.


This study

This study

  • This study uses a datamining approach to explore all block structure with in this network.


Characteristics

Characteristics

  • Genetic interaction:

    “Multiple genetic perturbations whose combination result in a phenotype that is unexpected given the phenotypes of the individual perturbations”

    The redundancies and dependencies within genetic network can provide powerful means for functional characterization.


Putting genetic interactions in context through a global modular decomposition

  • Unlike the PPI network, there is no obvious functional interpretation of a single genetic interaction, either negative or positive.

  • The genetic interaction of two genes does not imply that they interact physically, it simply suggest that they share some kind of functional interaction.


Modular hypothesis

Modular hypothesis

  • Gene membership falls into different type of functional modules

  • For example:

  • Protein complexes, pathways, etc.


Negative between pathway model

Negative between pathway Model

  • Defines Negative interactions: which are thought to arise between functionally redundant pathways such that deleting any pair of genes spanning across the pathways results in a significant reduction of fitness


Positive within pathway model

Positive within pathway Model

  • defines Positive interactions: If the second deletion in that same compromised pathway does not result in any additional fitness defect.


Bi clusters as block pattern in network

Bi-Clusters as block pattern in network

  • Can be over-lapping or disjoint sets of genes

  • Every gene in one set is connected to every other gene in other set.


Putting genetic interactions in context through a global modular decomposition

  • Pu et al.(2008) specifically designed an algorithm that randomly start with an initial bi-cluster and then rediscover the prominent bi-cluster many times.

  • In this study authors employed an approach based on an algorithm from field association rule mining to find all biclusters of sufficient size.


Approach summary bi cluster discovery

Approach Summary--bi-cluster Discovery

  • Recent data from Costanzo et al. (2010) was used in this study and the developed approach utilizes the apriori algorithm from the field of association rule mining to discover all biclusters.

  • and the biclusters that can be expressed by degree distribution alone were filter out using non-parametric statistical assessment.


Putting genetic interactions in context through a global modular decomposition

XMOD

  • This approach XMOD (eXhaustive Modular Discovery) guaranteed to find all bi-partite graphs : Where 1 part of bi-partite acts as a functional unit


Presence of degree distribution based bi clusters

Presence of degree distribution based Bi-clusters

  • Edges were randomized and still bi-partite graphs were obtained suggesting that biologically meaningless bipartite graphs can exist.

  • score for each bi-cluster lower for biologically meaningful

  • Score: “ the product of probabilities of each edge occurring independently conditioned on the degree of two interacting genes”


Putting genetic interactions in context through a global modular decomposition

  • Filtered Biclusters: using the independence score a cutt off is applied to separate the ones with less independence score

  • Condensed Biclusters: after removing Biclusters with >40% overlap


Comparison with other techniques

Comparison with other techniques


Dataset

Dataset

  • The dataset in Costanzoo et al. in 2010 was used.

  • 85,714 negative interactions and 35,858 interactions were used.


Association rule mining

Association rule Mining

  • Apriori Algorithm in Agrawal (1993) was used.

  • Its standard available implementation from a website was used.

  • Apriori was run on a binary set of positive interactions and also on a set of negative interactions


Randomizing the genetic interaction network

Randomizing the Genetic Interaction network

  • The number of edges for each gene was preserved but the targets were randomized.

  • A gene cannot have an edge with itself


Filtering random bi clusters

Filtering Random bi-clusters

  • We found that 50% of the real negative biclusters and 6% of real positive biclusters have scores below the 0.01 percentile of biclusters of the same size from the random networks. This resulted in 256,502 negative biclusters and 2194 positive biclusters.


Removing overlap from biclusters

Removing overlap from Biclusters

  • we first arranged the biclusters in descending order by area.

  • Then, beginning with the first bicluster A, we removed all biclusters whose area overlap with A was greater than 0.4, where overlap between biclusters A and B was calculated using the following formula:


Evaluation of functional coherence

Evaluation of Functional Coherence

MEFIT network is based on coexpression data and does not use genetic interaction datasets


Putting genetic interactions in context through a global modular decomposition

  • Improvements?


  • Login