[ { "id": "https://authors.library.caltech.edu/records/a6y6e-9dm30", "eprint_id": 96394, "eprint_status": "archive", "datestamp": "2023-08-19 19:43:03", "lastmod": "2023-10-20 21:08:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Siami-M", "name": { "family": "Siami", "given": "Milad" }, "orcid": "0000-0001-7253-4464" }, { "id": "Motee-N", "name": { "family": "Motee", "given": "Nader" }, "orcid": "0000-0002-0597-3659" }, { "id": "Buzi-G", "name": { "family": "Buzi", "given": "Gentian" }, "orcid": "0000-0002-8724-3405" }, { "id": "Bamieh-B", "name": { "family": "Bamieh", "given": "Bassam" }, "orcid": "0000-0001-9237-4613" }, { "id": "Khammash-K-H", "name": { "family": "Khammash", "given": "Mustafa" }, "orcid": "0000-0002-4855-9220" }, { "id": "Doyle-J-C", "name": { "family": "Doyle", "given": "John C." }, "orcid": "0000-0002-1828-2486" } ] }, "title": "Fundamental Limits and Tradeoffs in Autocatalytic Pathways", "ispublished": "pub", "full_text_status": "public", "keywords": "Biological networks, fundamental limits and tradeoffs, network analysis and control, nonlinear network analysis, optimal control, Robustness", "note": "\u00a9 2019 IEEE. \n\nManuscript received March 5, 2018; revised October 26, 2018 and April 22, 2019; accepted May 10, 2019. Date of publication June 7, 2019; date of current version January 28, 2020. \n\nM. Siami and N. Motee were in part supported by the NSF CAREER ECCS-1454022 and ONR YIP N00014-16-1-2645. B. Bamieh was in part supported by the NSF Award ECCS-1408442.\n\n
Submitted - 1706.09810.pdf
", "abstract": "This paper develops some basic principles to study autocatalytic networks and exploit their structural properties in order to characterize their inherent fundamental limits and tradeoffs. In a dynamical system with autocatalytic structure, the system's output is necessary to catalyze its own production. Our study has been motivated by a simplified model of a glycolysis pathway. First, the properties of this class of pathways are investigated through a network model, which consists of a chain of enzymatically catalyzed intermediate reactions coupled with an autocatalytic component. We explicitly derive a hard limit on the minimum achievable L\u2082-gain disturbance attenuation and a hard limit on its minimum required output energy. Then, we show how these resulting hard limits lead to some fundamental tradeoffs between transient and steady-state behavior of the network and its net production.", "date": "2020-02", "date_type": "published", "publication": "IEEE Transactions on Automatic Control", "volume": "65", "number": "2", "publisher": "IEEE", "pagerange": "733-740", "id_number": "CaltechAUTHORS:20190613-142206629", "issn": "0018-9286", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190613-142206629", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "ECCS-1454022" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-16-1-2645" }, { "agency": "NSF", "grant_number": "ECCS-1408442" } ] }, "doi": "10.1109/tac.2019.2921671", "primary_object": { "basename": "1706.09810.pdf", "url": "https://authors.library.caltech.edu/records/a6y6e-9dm30/files/1706.09810.pdf" }, "resource_type": "article", "pub_year": "2020", "author_list": "Siami, Milad; Motee, Nader; et el." }, { "id": "https://authors.library.caltech.edu/records/yt3z2-wa540", "eprint_id": 24390, "eprint_status": "archive", "datestamp": "2023-08-19 07:27:48", "lastmod": "2023-10-23 22:39:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chandra-F-A", "name": { "family": "Chandra", "given": "Fiona A." } }, { "id": "Buzi-G", "name": { "family": "Buzi", "given": "Gentian" }, "orcid": "0000-0002-8724-3405" }, { "id": "Doyle-J-C", "name": { "family": "Doyle", "given": "John C." }, "orcid": "0000-0002-1828-2486" } ] }, "title": "Glycolytic Oscillations and Limits on Robust Efficiency", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2011 American Association for the Advancement of Science. Received 22 November 2010; accepted 2 May 2011. The authors thank H. El-Samad and J. Stewart-Ornstein at the University of California, San Francisco, for their laboratory space and assistance; N. Pierce (Ray Deshaies' lab) for the green fluorescent protein library; O. Venturelli (Richard Murray's lab) for her help; and M. Csete for helpful feedback. Microscopy was performed at the Nikon Imaging Center at UCSF. Experimental data are available in SOM. This work is supported by the NIH (award R01GM078992A) and Institute of Collaborative Biotechnologies from the U.S. Army Research Office (subaward KK4102, prime award DAAD19-03-D-0004).", "abstract": "Both engineering and evolution are constrained by trade-offs between efficiency and robustness, but theory that formalizes this fact is limited. For a simple two-state model of glycolysis, we explicitly derive analytic equations for hard trade-offs between robustness and efficiency with oscillations as an inevitable side effect. The model describes how the trade-offs arise from individual parameters, including the interplay of feedback control with autocatalysis of network products necessary to power and catalyze intermediate reactions. We then use control theory to prove that the essential features of these hard trade-off \"laws\" are universal and fundamental, in that they depend minimally on the details of this system and generalize to the robust efficiency of any autocatalytic network. The theory also suggests worst-case conditions that are consistent with initial experiments.", "date": "2011-07-08", "date_type": "published", "publication": "Science", "volume": "333", "number": "6039", "publisher": "American Association for the Advancement of Science", "pagerange": "187-192", "id_number": "CaltechAUTHORS:20110712-150344607", "issn": "0036-8075", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110712-150344607", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01GM078992A" }, { "agency": "U. S. Army Research Office Insititute of Collaborative Biotechnologies subaward", "grant_number": "KK4102" }, { "agency": "U. S. Army Research Office Insititute of Collaborative Biotechnologies prime award", "grant_number": "DAAD19-03-D-0004" } ] }, "doi": "10.1126/science.1200705", "resource_type": "article", "pub_year": "2011", "author_list": "Chandra, Fiona A.; Buzi, Gentian; et el." }, { "id": "https://authors.library.caltech.edu/records/3stm3-sze21", "eprint_id": 24202, "eprint_status": "archive", "datestamp": "2023-08-22 02:48:31", "lastmod": "2023-10-23 20:23:02", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buzi-G", "name": { "family": "Buzi", "given": "Gentian" }, "orcid": "0000-0002-8724-3405" }, { "id": "Topcu-U", "name": { "family": "Topcu", "given": "Ufuk" } }, { "id": "Doyle-J-C", "name": { "family": "Doyle", "given": "John C." }, "orcid": "0000-0002-1828-2486" } ] }, "title": "Analysis of autocatalytic networks in biology", "ispublished": "pub", "full_text_status": "restricted", "keywords": "Autocatalytic pathways; Glycolysis; Quantitative analysis; Compositional analysis; Nonlinear systems", "note": "\u00a9 2011 Elsevier Ltd. \n\nReceived 1 February 2010; revised 21 January 2011; accepted 2 February 2011. Available online 21 March 2011. \n\nThis work was supported by the NIH (award# R01 GM078992A), the Institute of Collaborative Biotechnologies from the U.S. Army Research Office (UCSB award# KK9150, ARO prime award# W911NF-09-D-0001), and AFOSR (FA9550-08-1-0043). The material in this paper was partially presented at the 2010 American Control Conference, June 30\u2013July 2, 2010, Baltimore, Maryland, USA. This paper was recommended for publication in revised form by Associate Editor Elling Jacobsen under the direction of Editor Frank Allg\u00f6wer.", "abstract": "Autocatalytic networks, in particular the glycolytic pathway, constitute an important part of the cell metabolism. Changes in the concentration of metabolites and catalyzing enzymes during the lifetime of the cell can lead to perturbations from its nominal operating condition. We investigate the effects of such perturbations on stability properties, e.g., the extent of regions of attraction, of a particular family of autocatalytic network models. Numerical experiments demonstrate that systems that are robust with respect to perturbations in the parameter space have an easily \"verifiable\" (in terms of proof complexity) region of attraction properties. Motivated by the computational complexity of optimization-based formulations, we take a compositional approach and exploit a natural decomposition of the system, induced by the underlying biological structure, into a feedback interconnection of two input\u2013output subsystems: a small subsystem with complicating nonlinearities and a large subsystem with simple dynamics. This decomposition simplifies the analysis of large pathways by assembling region of attraction certificates based on the input\u2013output properties of the subsystems. It enables numerical as well as analytical construction of block-diagonal Lyapunov functions for a large family of autocatalytic pathways.", "date": "2011-06", "date_type": "published", "publication": "Automatica", "volume": "47", "number": "6", "publisher": "Elsevier", "pagerange": "1123-1130", "id_number": "CaltechAUTHORS:20110624-104150056", "issn": "0005-1098", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110624-104150056", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM078992A" }, { "agency": "Army Research Office (ARO)", "grant_number": "KK9150" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-09-D-0001" }, { "agency": "Air Force Office of Scientific Research (AFOSR)", "grant_number": "FA9550-08-1-0043" } ] }, "doi": "10.1016/j.automatica.2011.02.040", "resource_type": "article", "pub_year": "2011", "author_list": "Buzi, Gentian; Topcu, Ufuk; et el." }, { "id": "https://authors.library.caltech.edu/records/v3q97-9pr23", "eprint_id": 14516, "eprint_status": "archive", "datestamp": "2023-08-22 14:14:06", "lastmod": "2023-10-18 18:04:15", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "David-Fung-E-S", "name": { "family": "David-Fung", "given": "Elizabeth-Sharon" } }, { "id": "Butler-R", "name": { "family": "Butler", "given": "Robert" } }, { "id": "Buzi-G", "name": { "family": "Buzi", "given": "Gentian" }, "orcid": "0000-0002-8724-3405" }, { "id": "Yui-Mary-A", "name": { "family": "Yui", "given": "Mary A." }, "orcid": "0000-0002-3136-2181" }, { "id": "Diamond-R-A", "name": { "family": "Diamond", "given": "Rochelle A." } }, { "id": "Anderson-M-K", "name": { "family": "Anderson", "given": "Michele K." } }, { "id": "Rowen-L", "name": { "family": "Rowen", "given": "Lee" } }, { "id": "Rothenberg-E-V", "name": { "family": "Rothenberg", "given": "Ellen V." }, "orcid": "0000-0002-3901-347X" } ] }, "title": "Transcription factor expression dynamics of early T-lymphocyte specification and commitment", "ispublished": "pub", "full_text_status": "public", "keywords": "T-cell development; Notch; Thymus; Lineage commitment; Hematopoiesis", "note": "\u00a9 2009 Elsevier. \n\nReceived 16 September 2008; accepted 17 October 2008. Available online 5 November 2008. \n\nWe are deeply indebted to Dr. Howard Petrie (Scripps Florida) for valuable discussions during the gestation of this work and for generous sharing of data prior to publication. We are also grateful to Dr. Hamid Bolouri (Caltech and Institute for Systems Biology) and Dr. Eric Davidson (Caltech) for insightful critiques, encouragement, and advice. We also thank Brian Birditt and Scott Bloom (Institute for Systems Biology) for their excellent work sequencing and identifying the cDNA clones from our gene discovery; Marissa Morales and Dr. Rashmi Pant, for key contributions to the gene expression measurements and their validation; Dr. Tom Taghon, for generous collaboration on making the samples for the OP9 experiments; Gillian Giorgio, for early help curating the sequence files; Stephanie Adams of the Caltech Flow Cytometry Facility, for outstanding help with the sorting; and Robin Condie and Ruben Bayon for excellent care of the animals. \n\nThis work was undertaken with support from the Stowers Institute for Medical Research and then supported by grants from the NSF (MCB9983129) and the NIH (R01 CA90233 and R33 HL089123), and by the Louis A. Garfinkle Memorial Laboratory Fund, the Al Sherman Fund, the Albert Billings Ruddock Professorship, and the DNA Sequencer Royalty Fund at Caltech.\n\nAccepted Version - nihms92196.pdf
Supplemental Material - DAVdb09supp.doc
Supplemental Material - DAVdb09tableS1.doc
", "abstract": "Mammalian T lymphocytes are a prototype for development from adult pluripotent stem cells. While T-cell specification is driven by Notch signaling, T-lineage commitment is only finalized after prolonged Notch activation. However, no T-lineage specific regulatory factor has been reported that mediates commitment. We used a gene-discovery approach to identify additional candidate T-lineage transcription factors and characterized expression of > 100 regulatory genes in early T-cell precursors using realtime RT-PCR. These regulatory genes were also monitored in multilineage precursors as they entered T-cell or non-T-cell pathways in vitro; in non-T cells ex vivo; and in later T-cell developmental stages after lineage commitment. At least three major expression patterns were observed. Transcription factors in the largest group are expressed at relatively stable levels throughout T-lineage specification as a legacy from prethymic precursors, with some continuing while others are downregulated after commitment. Another group is highly expressed in the earliest stages only, and is downregulated before or during commitment. Genes in a third group undergo upregulation at one of three distinct transitions, suggesting a positive regulatory cascade. However, the transcription factors induced during commitment are not T-lineage specific. Different members of the same transcription factor family can follow opposite trajectories during specification and commitment, while factors co-expressed early can be expressed in divergent patterns in later T-cell development. Some factors reveal new regulatory distinctions between \u03b1\u03b2 and \u03b3\u03b4 T-lineage differentiation. These results show that T-cell identity has an essentially complex regulatory basis and provide a detailed framework for regulatory network modeling of T-cell specification.", "date": "2009-01-15", "date_type": "published", "publication": "Developmental Biology", "volume": "325", "number": "2", "publisher": "Elsevier", "pagerange": "444-467", "id_number": "CaltechAUTHORS:20090708-093942975", "issn": "0012-1606", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20090708-093942975", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Stowers Institute for Medical Research" }, { "agency": "NSF", "grant_number": "MCB9983129" }, { "agency": "NIH", "grant_number": "R01 CA90233" }, { "agency": "NIH", "grant_number": "R33 HL089123" }, { "agency": "Louis A. Garfinkle Memorial Laboratory Fund" }, { "agency": "Al Sherman Fund" }, { "agency": "Albert Billings Ruddock Professorship" }, { "agency": "DNA Sequencer Royalty Fund, Caltech" } ] }, "doi": "10.1016/j.ydbio.2008.10.021", "pmcid": "PMC2663971", "primary_object": { "basename": "DAVdb09supp.doc", "url": "https://authors.library.caltech.edu/records/v3q97-9pr23/files/DAVdb09supp.doc" }, "related_objects": [ { "basename": "DAVdb09tableS1.doc", "url": "https://authors.library.caltech.edu/records/v3q97-9pr23/files/DAVdb09tableS1.doc" }, { "basename": "nihms92196.pdf", "url": "https://authors.library.caltech.edu/records/v3q97-9pr23/files/nihms92196.pdf" } ], "resource_type": "article", "pub_year": "2009", "author_list": "David-Fung, Elizabeth-Sharon; Butler, Robert; et el." } ]