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Regulatory network reconstruction reveals genes with prognostic value for chronic lymphocytic leukemia

Overview of attention for article published in BMC Genomics, November 2015
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Title
Regulatory network reconstruction reveals genes with prognostic value for chronic lymphocytic leukemia
Published in
BMC Genomics, November 2015
DOI 10.1186/s12864-015-2189-6
Pubmed ID
Authors

Sally Yepes, Maria Mercedes Torres, Liliana López-Kleine

Abstract

The clinical course of chronic lymphocytic leukemia (CLL) is highly variable; some patients follow an indolent course, but others progress to a more advanced stage. The mutational status of rearranged immunoglobulin heavy chain variable (IGVH) genes in CLL is a feature that is widely recognized for dividing patients into groups that are related to their prognoses. However, the regulatory programs associated with the IGVH statuses are poorly understood, and markers that can precisely predict survival outcomes have yet to be identified. In this study, (i) we reconstructed gene regulatory networks in CLL by applying an information-theoretic approach to the expression profiles of 5 cohorts. (ii) We applied master regulator analysis (MRA) to these networks to identify transcription factors (TFs) that regulate an IGVH mutational status signature. The IGVH mutational status signature was developed by searching for differentially expressed genes between the IGVH mutational statuses in numerous CLL cohorts. (iii) To evaluate the biological implication of the inferred regulators, prognostic values were determined using time to treatment (TTT) and overall survival (OS) in two different cohorts. A robust IGVH expression signature was obtained, and various TFs emerged as regulators of the signature in most of the reconstructed networks. The TF targets expression profiles exhibited significant differences with respect to survival, which allowed the definition of a reduced profile with a high value for OS. TCF7 and its targets stood out for their roles in progression. TFs and their targets, which were obtained merely from inferred regulatory associations, have prognostic implications and reflect a regulatory context for prognosis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Austria 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 23%
Student > Master 8 20%
Student > Bachelor 5 13%
Unspecified 2 5%
Professor 2 5%
Other 9 23%
Unknown 5 13%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 28%
Agricultural and Biological Sciences 9 23%
Medicine and Dentistry 6 15%
Unspecified 2 5%
Engineering 2 5%
Other 3 8%
Unknown 7 18%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 September 2016.
All research outputs
#13,960,063
of 22,834,308 outputs
Outputs from BMC Genomics
#5,349
of 10,655 outputs
Outputs of similar age
#195,912
of 386,751 outputs
Outputs of similar age from BMC Genomics
#202
of 388 outputs
Altmetric has tracked 22,834,308 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 10,655 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 46th percentile – i.e., 46% of its peers scored the same or lower than it.
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We're also able to compare this research output to 388 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.