Richard A. Bonneau Associate Professor of Biology, Computer Science Ph.D. 2001 (Biochemistry), University of Washington; B.A. 1997 (Biochemistry), Florida State University. Office Address: New York University Department of Biology Center for Genomics and Systems Biology 12 Waverly Place, Room 406 New York, NY 10003 Email: Phone: (212) 992-9516 Fax: (212) 995-4015 List of Publications from Pubmed List of citations from Google Scholar Lab Homepage

Research

Biclustering / Transparent Probabilistic Data Integration: Grouping genes into functionally related and putatively co-regulated clusters is an essential first step for the inference of regulatory networks (one could think of many reasons for doing this but network inference is a good problem to start with). It is widely known that regulatory relationships among genes can vary under diverse environmental settings, and that co-expressed genes are trivially under control of the same regulator(s). This leads to patterns of co-expression that are valid under some, not all, observed conditions. With such considerations in mind, we have developed cMonkey, an unsupervised learning procedure for detecting putatively co-regulated gene clusters by integrating diverse systems biology data including: (1) mRNA and/or protein expression levels, (2) cis-regulatory sequences, and (3) functional association and physical interaction networks.

Network inference: We have also developed a methodology for deriving transcriptional regulatory interactions on a genomewide scale, and apply the method to predict a large portion of the gene regulatory network of the archaea, Halobacterium NRC-1. A small portion of the halobacterium learned network is shown below. The learned network is predictive, and was used to successfully predict the global expression of Halobacterium under novel perturbations (not part of the original training set) with predictive power similar to that seen over the training set. Methodological advancements over earlier work include an explicit treatment of time such that the network model can be fit using both steady-state measurements and heterogeneous time series simultaneously. The method contains a novel means for learning binary logic interactions between regulators that requires no discretization of data.

Rosetta de novo structure prediction: methods development for extracting functional information fro de novo structure predictions. Recent progress in de novo structure prediction methods has resulted in methods with increased accuracy that are applicable to greater numbers of proteins. When combined intelligently with other structure prediction methods, de novo structure prediction can contribute to systems biology in several ways. While still highly experimental such applications include 1) structural annotation on a genome wide scale and 2) synergy with experimental approaches to structural genomics such as the derivation of distance constraints from mass spectroscopy. I will describe the underlying methodologies common to current de novo prediction methods, focusing on core concepts rather than specific implementations, groups or methods. Possible applications of de novo structure prediction will also be reviewed. For more information, view our latest results on 80 complete genomes including many model organisms being actively studied at NYU. This work is being carried out in collaboration with David Baker.

Cytoscape: Cytoscape is a computer program designed to visualize systems biology data. This began initially as a program to map expression data onto networks and has evolved parallel to the field to encompass several other functionalities. We are involved in cytoscape development with a focus on providing immersive tools that can be used to view the data created by the HPF project (in collaboration with Iliana Avila-Campillo at the ISB). BioNetBuilder is a tool developed by Iliana to automatically build networks in cytoscape for any organism comprised of edges derived from protein-protein, protein-DNA, evolutionary comparison and metabolic/signaling pathways. For more information on Cytoscape see cytoscape.org.

Areas of Research/Interest

Systems Biology and Protein Modeling

Fellowships/Honors

Howard Hughes Medical Institute pre-doctoral Fellowship in the Biological Sciences, 1998-2001; Magna Cum Laude, Biochemistry, FSU, 1996; American Cancer Society – James Jay Fisher Fellowship, 1996; Florida Academic Scholars Award, 1993; International Baccalaureate Degree, 1993.

Publications

Integrated inference and analysis of regulatory networks from multi-level measurements. Methods Cell Biol   (2012) Poultney CS, Greenfield A, Bonneau R

Incorporation of noncanonical amino acids into Rosetta and use in computational protein-peptide interface design. PLoS One   (2012) Renfrew PD, Choi EJ, Bonneau R, Kuhlman B

Dynamic microRNA gene transcription and processing during T cell development. J Immunol   (2012 Apr 1) Kirigin FF, Lindstedt K, Sellars M, Ciofani M, Low SL, Jones L, Bell F, Pauli F, Bonneau R, Myers RM, Littman DR, Chong MM

The plant proteome folding project: structure and positive selection in plant protein families. Genome Biol Evol   (2012) Pentony MM, Winters P, Penfold-Brown D, Drew K, Narechania A, DeSalle R, Bonneau R, Purugganan MD

SlrA/SinR/SlrR inhibits motility gene expression upstream of a hypersensitive and hysteretic switch at the level of sigma(D) in Bacillus subtilis. Mol Microbiol   (2012 Mar) Cozy LM, Phillips AM, Calvo RA, Bate AR, Hsueh YH, Bonneau R, Eichenberger P, Kearns DB

N-Naphthyl peptoid foldamers exhibiting atropisomerism. Org Lett   (2012 Feb 3) Paul B, Butterfoss GL, Boswell MG, Huang ML, Bonneau R, Wolf C, Kirshenbaum K

Oligo(N-alkoxy glycines): trans substantiating peptoid conformations. Biopolymers   (2011) Jordan PA, Paul B, Butterfoss GL, Renfrew PD, Bonneau R, Kirshenbaum K

MODELING HOST-PATHOGEN INTERACTIONS: COMPUTATIONAL BIOLOGY AND BIOINFORMATICS FOR INFECTIOUS DISEASE RESEARCH. Pac Symp Biocomput   (2012) McDermott JE, Braun P, Bonneau R, Hyduke DR

Comparative microbial modules resource: generation and visualization of multi-species biclusters. PLoS Comput Biol   (2011 Dec) Kacmarczyk T, Waltman P, Bate A, Eichenberger P, Bonneau R

Rational design of temperature-sensitive alleles using computational structure prediction. PLoS One   (2011) Poultney CS, Butterfoss GL, Gutwein MR, Drew K, Gresham D, Gunsalus KC, Shasha DE, Bonneau R

The 2010 Rosetta developers meeting: macromolecular prediction and design meets reproducible publishing. PLoS One   (2011) Renfrew PD, Campbell G, Strauss CE, Bonneau R

The Proteome Folding Project: proteome-scale prediction of structure and function. Genome Res   (2011 Nov) Drew K, Winters P, Butterfoss GL, Berstis V, Uplinger K, Armstrong J, Riffle M, Schweighofer E, Bovermann B, Goodlett DR, Davis TN, Shasha D, Malmstrom L, Bonneau R

Peptoid atropisomers. J Am Chem Soc   (2011 Jul 20) Paul B, Butterfoss GL, Boswell MG, Renfrew PD, Yeung FG, Shah NH, Wolf C, Bonneau R, Kirshenbaum K

DREAM4: Combining genetic and dynamic information to identify biological networks and dynamical models. PLoS One   (2010) Greenfield A, Madar A, Ostrer H, Bonneau R

Multi-species integrative biclustering. Genome Biol   (2010) Waltman P, Kacmarczyk T, Bate AR, Kearns DB, Reiss DJ, Eichenberger P, Bonneau R

DREAM3: network inference using dynamic context likelihood of relatedness and the inferelator. PLoS One   (2010) Madar A, Greenfield A, Vanden-Eijnden E, Bonneau R

Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A   (2010 Feb 16) Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, Leaf IA, Aderem A

The Inferelator 2.0: a scalable framework for reconstruction of dynamic regulatory network models. Conf Proc IEEE Eng Med Biol Soc   (2009) Madar A, Greenfield A, Ostrer H, Vanden-Eijnden E, Bonneau R

A preliminary survey of the peptoid folding landscape. J Am Chem Soc   (2009 Nov 25) Butterfoss GL, Renfrew PD, Kuhlman B, Kirshenbaum K, Bonneau R

The coat morphogenetic protein SpoVID is necessary for spore encasement in Bacillus subtilis. Mol Microbiol   (2009 Nov) Wang KH, Isidro AL, Domingues L, Eskandarian HA, McKenney PT, Drew K, Grabowski P, Chua MH, Barry SN, Guan M, Bonneau R, Henriques AO, Eichenberger P

BioNetBuilder2.0: bringing systems biology to chicken and other model organisms. BMC Genomics   (2009) Konieczka JH, Drew K, Pine A, Belasco K, Davey S, Yatskievych TA, Bonneau R, Antin PB

2,5-Dimethyl-2,4-hexadiene induced photodechlorination of 9,10-dichloroanthracene. Photochem Photobiol Sci   (2009 Jun) Saltiel J, Smothers WK, Schanze KS, Charman SA, Bonneau R

Diurnally entrained anticipatory behavior in archaea. PLoS One   (2009) Whitehead K, Pan M, Masumura K, Bonneau R, Baliga NS

Learning global models of transcriptional regulatory networks from data. Methods Mol Biol   (2009) Madar A, Bonneau R

Oligo(N-aryl glycines): a new twist on structured peptoids. J Am Chem Soc   (2008 Dec 10) Shah NH, Butterfoss GL, Nguyen K, Yoo B, Bonneau R, Rabenstein DL, Kirshenbaum K

Learning biological networks: from modules to dynamics. Nat Chem Biol   (2008 Nov) Bonneau R

A protein domain-based interactome network for C. elegans early embryogenesis. Cell   (2008 Aug 8) Boxem M, Maliga Z, Klitgord N, Li N, Lemmens I, Mana M, de Lichtervelde L, Mul JD, van de Peut D, Devos M, Simonis N, Yildirim MA, Cokol M, Kao HL, de Smet AS, Wang H, Schlaitz AL, Hao T, Milstein S, Fan C, Tipsword M, Drew K, Galli M, Rhrissorrakrai K, Drechsel D, Koller D, Roth FP, Iakoucheva LM, Dunker AK, Bonneau R, Gunsalus KC, Hill DE, Piano F, Tavernier J, van den Heuvel S, Hyman AA, Vidal M

Dissecting the quorum-sensing receptor LuxN. Cell   (2008 Aug 8) Bonneau R

A predictive model for transcriptional control of physiology in a free living cell. Cell   (2007 Dec 28) Bonneau R, Facciotti MT, Reiss DJ, Schmid AK, Pan M, Kaur A, Thorsson V, Shannon P, Johnson MH, Bare JC, Longabaugh W, Vuthoori M, Whitehead K, Madar A, Suzuki L, Mori T, Chang DE, Diruggiero J, Johnson CH, Hood L, Baliga NS

Somatodendritic microRNAs identified by laser capture and multiplex RT-PCR. RNA   (2007 Aug) Kye MJ, Liu T, Levy SF, Xu NL, Groves BB, Bonneau R, Lao K, Kosik KS

Superfamily assignments for the yeast proteome through integration of structure prediction with the gene ontology. PLoS Biol   (2007 Apr) Malmstrom L, Riffle M, Strauss CE, Chivian D, Davis TN, Bonneau R, Baker D

General transcription factor specified global gene regulation in archaea. Proc Natl Acad Sci U S A   (2007 Mar 13) Facciotti MT, Reiss DJ, Pan M, Kaur A, Vuthoori M, Bonneau R, Shannon P, Srivastava A, Donohoe SM, Hood LE, Baliga NS

A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. J Exp Med   (2007 Feb 19) Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A

BioNetBuilder: automatic integration of biological networks. Bioinformatics   (2007 Feb 1) Avila-Campillo I, Drew K, Lin J, Reiss DJ, Bonneau R

Quantitative proteomic analysis of the budding yeast cell cycle using acid-cleavable isotope-coded affinity tag reagents. Proteomics   (2006 Dec) Flory MR, Lee H, Bonneau R, Mallick P, Serikawa K, Morris DR, Aebersold R

UniPep--a database for human N-linked glycosites: a resource for biomarker discovery. Genome Biol   (2006) Zhang H, Loriaux P, Eng J, Campbell D, Keller A, Moss P, Bonneau R, Zhang N, Zhou Y, Wollscheid B, Cooke K, Yi EC, Lee H, Peskind ER, Zhang J, Smith RD, Aebersold R

Integrated biclustering of heterogeneous genome-wide datasets for the inference of global regulatory networks. BMC Bioinformatics   (2006) Reiss DJ, Baliga NS, Bonneau R

The Inferelator: an algorithm for learning parsimonious regulatory networks from systems-biology data sets de novo. Genome Biol   (2006) Bonneau R, Reiss DJ, Shannon P, Facciotti M, Hood L, Baliga NS, Thorsson V

The Gaggle: an open-source software system for integrating bioinformatics software and data sources. BMC Bioinformatics   (2006) Shannon PT, Reiss DJ, Bonneau R, Baliga NS

THUMP: an immersive haptic console for surgical simulation and training. Stud Health Technol Inform   (2004) Niemeyer G, Kuchenbecker KJ, Bonneau R, Mitra P, Reid AM, Fiene J, Weldon G

Genome sequence of Haloarcula marismortui: a halophilic archaeon from the Dead Sea. Genome Res   (2004 Nov) Baliga NS, Bonneau R, Facciotti MT, Pan M, Glusman G, Deutsch EW, Shannon P, Chiu Y, Weng RS, Gan RR, Hung P, Date SV, Marcotte E, Hood L, Ng WV

Systems approaches applied to the study of Saccharomyces cerevisiae and Halobacterium sp. Cold Spring Harb Symp Quant Biol   (2003) Weston AD, Baliga NS, Bonneau R, Hood L

Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1. Genome Biol   (2004) Bonneau R, Baliga NS, Deutsch EW, Shannon P, Hood L

Systems level insights into the stress response to UV radiation in the halophilic archaeon Halobacterium NRC-1. Genome Res   (2004 Jun) Baliga NS, Bjork SJ, Bonneau R, Pan M, Iloanusi C, Kottemann MC, Hood L, DiRuggiero J

Automated prediction of CASP-5 structures using the Robetta server. Proteins   (2003) Chivian D, Kim DE, Malmstrom L, Bradley P, Robertson T, Murphy P, Strauss CE, Bonneau R, Rohl CA, Baker D

An improved protein decoy set for testing energy functions for protein structure prediction. Proteins   (2003 Oct 1) Tsai J, Bonneau R, Morozov AV, Kuhlman B, Rohl CA, Baker D

Photoprotodesilylation of 9-trimethylsilylanthracene in alcohols. Photochem Photobiol Sci   (2003 Mar) Desvergne JP, Bonneau R, Dorr G, Bouas-Laurent H

Ab initio methods. Methods Biochem Anal   (2003) Chivian D, Robertson T, Bonneau R, Baker D

Zinc status modulates bronchopulmonary eosinophil infiltration in a murine model of allergic inflammation. Chest   (2003 Mar) Richter M, Bonneau R, Girard MA, Beaulieu C, Larivee P

De novo prediction of three-dimensional structures for major protein families. J Mol Biol   (2002 Sep 6) Bonneau R, Strauss CE, Rohl CA, Chivian D, Bradley P, Malmstrom L, Robertson T, Baker D

Contact order and ab initio protein structure prediction. Protein Sci   (2002 Aug) Bonneau R, Ruczinski I, Tsai J, Baker D

Distributions of beta sheets in proteins with application to structure prediction. Proteins   (2002 Jul 1) Ruczinski I, Kooperberg C, Bonneau R, Baker D

Rosetta in CASP4: progress in ab initio protein structure prediction. Proteins   (2001) Bonneau R, Tsai J, Ruczinski I, Chivian D, Rohl C, Strauss CE, Baker D

Photochemistry of methoxyhydroquinone and methoxy-p-benzoquinone in solution related to the photoyellowing of the lignocellulosics. Photochem Photobiol   (2001 Oct) Bearnais-Barbry S, Bonneau R, Castellan A

Functional inferences from blind ab initio protein structure predictions. J Struct Biol   (2001 May-Jun) Bonneau R, Tsai J, Ruczinski I, Baker D

Ab initio protein structure prediction: progress and prospects. Annu Rev Biophys Biomol Struct   (2001) Bonneau R, Baker D

Improving the performance of Rosetta using multiple sequence alignment information and global measures of hydrophobic core formation. Proteins   (2001 Apr 1) Bonneau R, Strauss CE, Baker D

Ab initio protein structure prediction of CASP III targets using ROSETTA. Proteins   (1999) Simons KT, Bonneau R, Ruczinski I, Baker D

Spatial distribution of DNA ploidy in colorectal carcinoma. Anal Cell Pathol   (1994 Dec) Bigras G, Bonneau R, Dumont A

[No title available] Can Fam Physician   (1992 Sep) Bonneau R

Plexiform fibrohistiocytic tumor. Dermatologica   (1991) Giard F, Bonneau R, Raymond GP

[Merkel's tumor]. Union Med Can   (1984 Jun) Bonneau R, Bluteau P

[Is Goodpasture's syndrome always a triad?]. Union Med Can   (1984 Jan) Bonneau R, Giroux L

Neuromuscular choristoma. A clinicopathologic study of two cases. Am J Surg Pathol   (1983 Sep) Bonneau R, Brochu P