Intrachromosomal regulation decay in breast cancer

Anda-Jáuregui, Guillermo de; Fresno, Cristóbal; García-Cortés, Diana; Espinal-Enríquez, Jesús; Hernández‐Lemus, Enrique

doi:10.2478/amns.2019.1.00020

Cited by 16 publications

(21 citation statements)

References 22 publications

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“…decay in all cancer phenotypes is similar to that showed by our group for Basal breast cancer (43). There, co-expression strength diminished with distance in an exponential-like form.…”

Section: Co-expression Decay Associated To Distance Is Specific For Esupporting

confidence: 88%

Gene Co-expression Is Distance-Dependent in Breast Cancer

et al. 2020

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Breast carcinomas are characterized by anomalous gene regulatory programs. As is well-known, gene expression programs are able to shape phenotypes. Hence, the understanding of gene co-expression may shed light on the underlying mechanisms behind the transcriptional regulatory programs affecting tumor development and evolution. For instance, in breast cancer, there is a clear loss of inter-chromosomal (trans-) co-expression, compared with healthy tissue. At the same time cis-(intra-chromosomal) interactions are favored in breast tumors. In order to have a deeper understanding of regulatory phenomena in cancer, here, we constructed Gene Co-expression Networks by using TCGA-derived RNA-seq whole-genome samples corresponding to the four breast cancer molecular subtypes, as well as healthy tissue. We quantify the cis-/trans-co-expression imbalance in all phenotypes. Additionally, we measured the association between co-expression and physical distance between genes, and characterized the ratio of intra/inter-cytoband interactions per phenotype. We confirmed loss of trans-co-expression in all molecular subtypes. We also observed that gene cis-co-expression decays abruptly with distance in all tumors in contrast with healthy tissue. We observed co-expressed gene hotspots, that tend to be connected at cytoband regions, and coincide accurately with already known copy number altered regions, such as Chr17q12, or Chr8q24.3 for all subtypes. Our methodology recovered different alterations already reported for specific breast cancer subtypes, showing how co-expression network approaches might help to capture distinct events that modify the cell regulatory program.

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“…decay in all cancer phenotypes is similar to that showed by our group for Basal breast cancer (43). There, co-expression strength diminished with distance in an exponential-like form.…”

Section: Co-expression Decay Associated To Distance Is Specific For Esupporting

confidence: 88%

Gene Co-expression Is Distance-Dependent in Breast Cancer

et al. 2020

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“…The ANOVA table results are presented in Supplementary Table 1, which confirms the distance-dependent decay in breast cancer subtypes (P <1e-4)). The shape of this decay in all cancer phenotypes is similar to that showed by our group for basal breast cancer [31]. There, co-expression strength diminished with distance in an exponential-like form.…”

Section: Cis-/trans-imbalance Is a Common Feature In Breast Cancer Susupporting

confidence: 85%

Gene co-expression is distance-dependent in breast cancer

García-Cortés

Anda-Jáuregui²,

Fresno³

et al. 2018

Preprint

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Breast carcinomas are characterized by anomalous gene regulatory programs. As is well known, gene expression programs are able to shape phenotypes. Hence, the understanding of gene co-expression may shed light on the underlying mechanisms behind the transcriptional regulatory programs affecting tumor development and evolution. For instance, in breast cancer, there is a clear loss of inter-chromosomal (trans-) co-expression, compared with healthy tissue. At the same time cis-(intrachromosomal) interactions are favored in breast tumors. In order to have a deeper understanding of regulatory phenomena in cancer, here, we constructed Gene Coexpression Networks by using 848 RNA-seq whole-genome samples corresponding to the four breast cancer molecular subtypes, as well as healthy tissue. We quantify the cis-/trans-co-expression imbalance in all phenotypes. Additionally, we measured the association between co-expression and physical distance between genes, and characterized the proportion of intra/inter-cytoband interactions per phenotype. We confirmed loss of trans-co-expression in all molecular subtypes. We also observed that gene cis-co-expression decays abruptly with distance in all tumors in contrast with healthy tissue. We observed co-expressed gene hotspots, that tend to be connected at cytoband regions, and coincide accurately with already known copy number altered regions, such as Chr17q12, or Chr8q24.3 for all subtypes. Our methodology recovered different alterations already reported for specific breast cancer subtypes, showing how co-expression network approaches might help to capture distinct events that modify the cell regulatory program.

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“…Previously [6][7][8], we observed that in breast cancer, trans-(inter-chromosome) gene interactions are more scarce and weaker in cancer samples compared to the healthy phenotype. Furthermore, in breast cancer, cis-interactions become stronger, however, this is strongest between physically close genes, and this gene correlation strength decays with the distance.…”

Section: Spatial Anomalies In Cancer-associated Grpsmentioning

confidence: 83%

“…Following previous work [7], we define a gene regulatory program (GRP) as a graph G[I(X i , X j )] of all the mutual information functions for a given empirical transcriptomics sampling space Ω. It can be shown that G[I(X i , X j )] is indeed a Markov random field [11,12] considering mutual information distributions under the pairwise sufficiency assumption [13].…”

Section: An Information Theoretical Approach To Gene Regulatory Programsmentioning

confidence: 99%

“…, we identify that interchromosomal interactions between genes in any pair of chromosomes have more losses than gains of MI in disease, with an average MI loss greater than the average MI gain. Meanwhile, intrachromosomal interactions may exhibit three different behaviors: (i) they have more losses with higher average MI loss, although with higher GLS and GLR values than the interchromosomal interactions (chromosomes 1, 2, 5, 6, 11, 17, 19, X); (ii) they have more losses, but the average MI gain is higher (chromosomes 3,4,7,8,9,10,12,13,14,15,16,18,19,20,22) or (iii) they have more gains, with a higher average MI gain (21).…”

Section: Intra-and Inter-chromosome Interactions Exhibit Differences mentioning

confidence: 99%

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Spatial Organization of the Gene Regulatory Program: An Information Theoretical Approach to Breast Cancer Transcriptomics

Anda-Jáuregui

Espinal-Enríquez

Hernández‐Lemus

2019

Entropy

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Gene regulation may be studied from an information-theoretic perspective. Gene regulatory programs are representations of the complete regulatory phenomenon associated to each biological state. In diseases such as cancer, these programs exhibit major alterations, which have been associated with the spatial organization of the genome into chromosomes. In this work, we analyze intrachromosomal, or cis-, and interchromosomal, or trans-gene regulatory programs in order to assess the differences that arise in the context of breast cancer. We find that using information theoretic approaches, it is possible to differentiate cis-and trans-regulatory programs in terms of the changes that they exhibit in the breast cancer context, indicating that in breast cancer there is a loss of trans-regulation. Finally, we use these programs to reconstruct a possible spatial relationship between chromosomes.

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Intrachromosomal regulation decay in breast cancer

Cited by 16 publications

References 22 publications

Gene Co-expression Is Distance-Dependent in Breast Cancer

Gene Co-expression Is Distance-Dependent in Breast Cancer

Gene co-expression is distance-dependent in breast cancer

Spatial Organization of the Gene Regulatory Program: An Information Theoretical Approach to Breast Cancer Transcriptomics

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