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Annals of Translational Medicine
Article . 2019 . Peer-reviewed
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Annals of Translational Medicine
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Gene-gene interaction: the curse of dimensionality

Authors: Amrita, Chattopadhyay; Tzu-Pin, Lu;

Gene-gene interaction: the curse of dimensionality

Abstract

Identified genetic variants from genome wide association studies frequently show only modest effects on the disease risk, leading to the "missing heritability" problem. An avenue, to account for a part of this "missingness" is to evaluate gene-gene interactions (epistasis) thereby elucidating their effect on complex diseases. This can potentially help with identifying gene functions, pathways, and drug targets. However, the exhaustive evaluation of all possible genetic interactions among millions of single nucleotide polymorphisms (SNPs) raises several issues, otherwise known as the "curse of dimensionality". The dimensionality involved in the epistatic analysis of such exponentially growing SNPs diminishes the usefulness of traditional, parametric statistical methods. With the immense popularity of multifactor dimensionality reduction (MDR), a non-parametric method, proposed in 2001, that classifies multi-dimensional genotypes into one- dimensional binary approaches, led to the emergence of a fast-growing collection of methods that were based on the MDR approach. Moreover, machine-learning (ML) methods such as random forests and neural networks (NNs), deep-learning (DL) approaches, and hybrid approaches have also been applied profusely, in the recent years, to tackle this dimensionality issue associated with whole genome gene-gene interaction studies. However, exhaustive searching in MDR based approaches or variable selection in ML methods, still pose the risk of missing out on relevant SNPs. Furthermore, interpretability issues are a major hindrance for DL methods. To minimize this loss of information, Python based tools such as PySpark can potentially take advantage of distributed computing resources in the cloud, to bring back smaller subsets of data for further local analysis. Parallel computing can be a powerful resource that stands to fight this "curse". PySpark supports all standard Python libraries and C extensions thus making it convenient to write codes to deliver dramatic improvements in processing speed for extraordinarily large sets of data.

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
41
Top 10%
Top 10%
Top 10%
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