TFInfer: a tool for probabilistic inference of transcription factor activities

Asif, Hafiz M.; Rolfe, Matthew D.; Green, Jeff; Lawrence, Neil D.; Rattray, Magnus; Sanguinetti, Guido

doi:10.1093/bioinformatics/btq469

Cited by 24 publications

(52 citation statements)

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“…Black bars indicate upregulation, and gray bars indicate downregulation. using the TFInfer statistical software suite (3). Given microarray data from E. coli grown under aerobic or anaerobic conditions and either in the presence or in the absence of CORM-3 or iCORM-3, TFInfer returns the probability distributions for the activity of each TF, as well as the strengths of the TF-target interactions (see the Materials and Methods section).…”

Section: Mclean Et Almentioning

confidence: 99%

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Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Mclean

Begg

Jesse

et al. 2013

Antioxidants & Redox Signaling

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Aims: Carbon monoxide (CO)-releasing molecules (CO-RMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically. One such application is antimicrobial activity; therefore, we aimed to characterize and compare the effects of the CO-RM, CORM-3, and its inactivated counterpart, where all labile CO has been removed, at the transcriptomic and cellular level. Results: We found that both compounds are able to penetrate the cell, but the inactive form is not inhibitory to bacterial growth under conditions where CORM-3 is. Transcriptomic analyses revealed that the bacterial response to inactivated CORM-3 (iCORM-3) is much lower than to the active compound and that a wide range of processes appear to be affected by CORM-3 and to a lesser extent iCORM-3, including energy metabolism, membrane transport, motility, and the metabolism of many sulfur-containing species, including cysteine and methionine. Innovation: This work has demonstrated that both CORM-3 and its inactivated counterpart react with cellular functions to yield a complex response at the transcriptomic level. A full understanding of the actions of both compounds is vital to understand the toxic effects of CO-RMs. Conclusion: This work has furthered our understanding of how CORM-3 behaves at the cellular level and identifies the responses that occur when the host is exposed to the Ru compound as well as those that result from the released CO. This is a vital step in laying the groundwork for future development of optimized CO-RMs for eventual use in antimicrobial therapy.

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Section: Mclean Et Almentioning

confidence: 99%

“…Ru(CO) 3 Cl(glycinate), more commonly known as CORM-3, is a water-soluble Ru-containing compound, capable of releasing one CO per molecule with a half-life of *2 min in vitro (8,28). CORM-3 is bactericidal against a variety of microbes, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (10,12,13,30,40).…”

mentioning

confidence: 99%

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Mclean

Begg

Jesse

et al. 2013

Antioxidants & Redox Signaling

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“…In addition to the changes in transcript abundance that pass an arbitrary ≥ threefold ( t ‐test, P = 0.05) filter (Table 2), there were widespread changes that are components of the transcriptional response that sit below this statistical filter. To capture the breadth of the transcriptional response when the anaerobic fermentative system was perturbed by introduction of the primary signal TMAO, the activities of 167 TFs that are recorded as able to directly regulate target genes in the EcoCyc database (Keseler et al ., 2013) were simultaneously inferred from the transcript profiles using the open access tfinfer software (Asif et al ., 2010). tfinfer is based on a state space model that employs a linear approximation (in log space) to the dynamics of transcription and treats noise in a principled way such that the estimated TF activities are associated with confidence limits (Sanguinetti et al ., 2006).…”

Section: Resultsmentioning

confidence: 99%

“…coli by switching to TMAO ‐respiratory/fermentative metabolism. ( A ) The output from the tfinfer software ( A sif et al ., 2010) at the indicated times (minutes) after TMAO (46 m M ) addition to anaerobic fermentative steady‐state cultures. Each cell is coloured to provide a visual representation of the TF activities inferred from the complete transcript profile dataset as follows: TF activity 0–1, blue; 1–2, green; 2–3, yellow; 3–4, orange; > 4, red.…”

Section: Resultsmentioning

confidence: 99%

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Adaptation of anaerobic cultures of Escherichia coli K‐12 in response to environmental trimethylamine‐N‐oxide

Denby

Rolfe

Crick

et al. 2015

Environmental Microbiology

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SummarySystematic analyses of transcriptional and metabolic changes occurring when E scherichia coli K‐12 switches from fermentative growth to anaerobic respiratory growth with trimethylamine‐N‐oxide (TMAO) as the terminal electron acceptor revealed: (i) the induction of torCAD, but not genes encoding alternative TMAO reductases; (ii) transient expression of frmRAB, encoding formaldehyde dehydrogenase; and (iii) downregulation of copper resistance genes. Simultaneous inference of 167 transcription factor (TF) activities implied that transcriptional re‐programming was mediated by 20 TFs, including the transient inactivation of the two‐component system ArcBA; a prediction validated by direct measurement of phosphorylated ArcA. Induction of frmRAB, detection of dimethylamine in culture medium and formaldehyde production when cell‐free extracts were incubated with TMAO suggested the presence of TMAO demethylase activity. Accordingly, the viability of an frmRAB mutant was compromised upon exposure to TMAO. Downregulation of genes involved in copper resistance could be accounted for by TMAO inhibition of Cu(II) reduction. The simplest interpretation of the data is that during adaptation to the presence of environmental TMAO, anaerobic fermentative cultures of E . coli respond by activating the TorTSR regulatory system with consequent induction of TMAO reductase activity, resulting in net oxidation of menaquinone and inhibition of Cu(II) reduction, responses that are sensed by ArcBA and CusRS respectively.

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Structures of the TetR‐like transcription regulator RcdA alone and in complexes with ligands

Pietrzyk‐Brzezinska

Cociurovscaia

2021

Proteins

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RcdA is a helix‐turn‐helix (HTH) transcriptional regulator belonging to the TetR family. The protein regulates the transcription of curlin subunit gene D, the master regulator of biofilm formation. Moreover, it was predicted that it might be involved in the regulation of up to 27 different genes. However, an effector of RcdA and the environmental conditions which trigger RcdA action remain unknown. Herein, we report the first crystal structures of RcdA in complexes with ligands, trimethylamine N‐oxide (TMAO) and tris(hydroxymethyl)aminomethane (Tris), which might serve as RcdA effectors. Based on these structures, the ligand‐binding pocket of RcdA was characterized in detail. The conservation of the amino acid residues forming the ligand‐binding cavity was analyzed and the comprehensive search for RcdA structural homologs was performed. This analysis indicated that RcdA is structurally similar to multidrug‐binding TetR family members, however, its ligand‐binding cavity differs significantly from the pockets of its structural homologs. The interaction of RcdA with TMAO and Tris indicates that the protein might be involved in alkaline stress response.

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TFInfer: a tool for probabilistic inference of transcription factor activities

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 24 publications

References 5 publications

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Adaptation of anaerobic cultures of Escherichia coli K‐12 in response to environmental trimethylamine‐N‐oxide

Structures of the TetR‐like transcription regulator RcdA alone and in complexes with ligands

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TFInfer: a tool for probabilistic inference of transcription factor activities

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 24 publications

References 5 publications

Analysis of the Bacterial Response to Ru(CO)3Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Analysis of the Bacterial Response to Ru(CO)3Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Adaptation of anaerobic cultures of Escherichia coli K‐12 in response to environmental trimethylamine‐N‐oxide

Structures of the TetR‐like transcription regulator RcdA alone and in complexes with ligands

Contact Info

Product

Resources

About

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action