Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method

<p>Abstract</p> <p>Background</p> <p>The importance of <it>in silico </it>predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular...

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Main Authors: Inestrosa Nibaldo C, Martínez Servet, Pavez Leonardo, González Mauricio, Aravena Andrés, Colombres Marcela, Assar Rodrigo, Hödar Christian, Maass Alejandro
Format: Article
Language:English
Published: BMC 2010-06-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/11/348
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spelling doaj-95f3e781ed8143d08793258afaa35d282020-11-24T20:49:15ZengBMCBMC Genomics1471-21642010-06-0111134810.1186/1471-2164-11-348Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART methodInestrosa Nibaldo CMartínez ServetPavez LeonardoGonzález MauricioAravena AndrésColombres MarcelaAssar RodrigoHödar ChristianMaass Alejandro<p>Abstract</p> <p>Background</p> <p>The importance of <it>in silico </it>predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of <it>cis </it>regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/β-catenin pathway target genes potentially involved in brain diseases.</p> <p>Results</p> <p>In this study, we propose 89 new Wnt/β-catenin pathway target genes predicted <it>in silico </it>by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/β-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid β toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway.</p> <p>Conclusions</p> <p>Our multiple CART strategy proved to be an effective tool to identify new Wnt/β-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders.</p> http://www.biomedcentral.com/1471-2164/11/348
collection DOAJ
language English
format Article
sources DOAJ
author Inestrosa Nibaldo C
Martínez Servet
Pavez Leonardo
González Mauricio
Aravena Andrés
Colombres Marcela
Assar Rodrigo
Hödar Christian
Maass Alejandro
spellingShingle Inestrosa Nibaldo C
Martínez Servet
Pavez Leonardo
González Mauricio
Aravena Andrés
Colombres Marcela
Assar Rodrigo
Hödar Christian
Maass Alejandro
Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
BMC Genomics
author_facet Inestrosa Nibaldo C
Martínez Servet
Pavez Leonardo
González Mauricio
Aravena Andrés
Colombres Marcela
Assar Rodrigo
Hödar Christian
Maass Alejandro
author_sort Inestrosa Nibaldo C
title Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
title_short Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
title_full Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
title_fullStr Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
title_full_unstemmed Genome-wide identification of new Wnt/β-catenin target genes in the human genome using CART method
title_sort genome-wide identification of new wnt/β-catenin target genes in the human genome using cart method
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2010-06-01
description <p>Abstract</p> <p>Background</p> <p>The importance of <it>in silico </it>predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of <it>cis </it>regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/β-catenin pathway target genes potentially involved in brain diseases.</p> <p>Results</p> <p>In this study, we propose 89 new Wnt/β-catenin pathway target genes predicted <it>in silico </it>by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/β-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid β toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway.</p> <p>Conclusions</p> <p>Our multiple CART strategy proved to be an effective tool to identify new Wnt/β-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders.</p>
url http://www.biomedcentral.com/1471-2164/11/348
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