On 2015 May 19, L Charles Murtaugh commented:

The basis of this paper will be somewhat confusing to those who adhere to the traditional definition of "transcription factor," as a DNA-binding protein that regulates gene transcription (http://www.nature.com/scitable/definition/general-transcription-factor-transcription-factor-167). Not one of the genes mentioned in the abstract is a transcription factor, by the conventional definition; instead, all of them are regulators of DNA synthesis or other aspects of cell cycle progression. In fact, only one of the 20 top "transcription factors" described as differentially-expressed in this study (Tables 3 and 4), Xbp1, is an actual transcription factor. I must question, therefore, the validity of the dense transcriptional regulatory networks presented in Figures 3-4 of this paper.

One culprit here seems to be the authors' uncritical acceptance of a previous study (http://www.ncbi.nlm.nih.gov/pubmed/18713790) that purported to establish a comprehensive database of mammalian transcription factors. Again, a cursory examination of this database (http://itfp.biosino.org/itfp/TFViewer/human_tf.jsp?table=human_tf&page=1) reveals that the majority of its members are not transcription factors at all. Indeed, the fact that this previous manuscript suggested the existence of >4000 human TFs, 2-3 times more than conventional estimates, should have raised red flags not only for its original peer reviewers, but also for authors of the current study.

On 2015 May 19, L Charles Murtaugh commented:

The basis of this paper will be somewhat confusing to those who adhere to the traditional definition of "transcription factor," as a DNA-binding protein that regulates gene transcription (http://www.nature.com/scitable/definition/general-transcription-factor-transcription-factor-167). Not one of the genes mentioned in the abstract is a transcription factor, by the conventional definition; instead, all of them are regulators of DNA synthesis or other aspects of cell cycle progression. In fact, only one of the 20 top "transcription factors" described as differentially-expressed in this study (Tables 3 and 4), Xbp1, is an actual transcription factor. I must question, therefore, the validity of the dense transcriptional regulatory networks presented in Figures 3-4 of this paper.

One culprit here seems to be the authors' uncritical acceptance of a previous study (http://www.ncbi.nlm.nih.gov/pubmed/18713790) that purported to establish a comprehensive database of mammalian transcription factors. Again, a cursory examination of this database (http://itfp.biosino.org/itfp/TFViewer/human_tf.jsp?table=human_tf&page=1) reveals that the majority of its members are not transcription factors at all. Indeed, the fact that this previous manuscript suggested the existence of >4000 human TFs, 2-3 times more than conventional estimates, should have raised red flags not only for its original peer reviewers, but also for authors of the current study.