DOI: 10.1073/pnas.0407365101. Interacting models of cooperative gene regulation

Interacting models of cooperative gene regulation

10.1073/pnas.0407365101

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Cooperativity between transcription factors is critical to gene regulation. Current computational methods do not take adequate account of this salient aspect. To address this issue, we present a computational method based on multivariate adaptive regression splines to correlate the occurrences of transcription factor binding motifs in the promoter DNA and their interactions to the logarithm of the ratio of gene expression levels. This allows us to discover both the individual motifs and synergistic pairs of motifs that are most likely to be functional, and enumerate their relative contributions at any arbitrary time point for which mRNA expression data are available. We present results of simulations and focus specifically on the yeast cell-cycle data. Inclusion of synergistic interactions can increase the prediction accuracy over linear regression to as much as 1.5- to 3.5-fold. Significant motifs and combinations of motifs are appropriately predicted at each stage of the cell cycle. We believe our multivariate adaptive regression splines-based approach will become more significant when applied to higher eukaryotes, especially mammals, where cooperative control of gene regulation is absolutely essential.

Bibliography

Das, D., Banerjee, N., & Zhang, M. Q. (2004). Interacting models of cooperative gene regulation. Proceedings of the National Academy of Sciences, 101(46), 16234â16239.

Authors 3

Debopriya Das (first)
Nilanjana Banerjee (additional)
Michael Q. Zhang (additional)

References 29 Referenced 91

10.1038/nature01763
10.1016/S0092-8674(00)80893-4
10.1091/mbc.9.12.3273
10.1038/84792
10.1073/pnas.0630591100
10.1038/ng724
10.1093/nar/gkg894
10.1093/bioinformatics/btg480
10.1093/bioinformatics/18.9.1167
10.1186/gb-2003-4-7-r43
Friedman, J. H. (1991) Ann. Stat. 19, 1-67. / Ann. Stat. (1991)
Hastie T. Tibshirani R. & Friedman J. H. (2001) The Elements of Statistical Learning (Springer New York). (10.1007/978-0-387-21606-5)
Steinberg D. & Colla P. (1999) MARS: An Introduction (Salford Systems San Diego).
10.1038/nature01644
Press W. H. Flannery B. P. Teukolsky S. A. & Vetterling W. T. (1992) Numerical Recipes in C: The Art of Scientific Computing (Cambridge Univ. Press Cambridge U. K.).
Benjamini, Y. & Hochberg, Y. (1995) J. R. Stat. Soc. B 57, 289-300. (10.1111/j.2517-6161.1995.tb02031.x) / J. R. Stat. Soc. B (1995)
10.1016/S1097-2765(00)80114-8
10.1016/S0092-8674(01)00494-9
10.1091/mbc.10.10.3301
10.1128/MCB.16.6.2830
10.1038/35017581
10.1101/gad.1034302
10.1128/MCB.22.2.430-441.2002
10.1101/gr.9.11.1040
10.1093/genetics/165.3.1017
10.1101/gr.301202
10.1002/j.1460-2075.1995.tb00270.x
10.1093/nar/gkg200
10.1101/gr.1271603

Dates

Type	When
Created	20 years, 9 months ago (Nov. 8, 2004, 8:25 p.m.)
Deposited	8 months, 2 weeks ago (Dec. 19, 2024, 3:57 p.m.)
Indexed	1 month, 3 weeks ago (July 11, 2025, 9:10 p.m.)
Issued	20 years, 9 months ago (Nov. 8, 2004)
Published	20 years, 9 months ago (Nov. 8, 2004)
Published Online	20 years, 9 months ago (Nov. 8, 2004)
Published Print	20 years, 9 months ago (Nov. 16, 2004)

Funders 0

None

BibTeX

@article{Das_2004, title={Interacting models of cooperative gene regulation}, volume={101}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0407365101}, DOI={10.1073/pnas.0407365101}, number={46}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Das, Debopriya and Banerjee, Nilanjana and Zhang, Michael Q.}, year={2004}, month=nov, pages={16234–16239} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        12
      ]
    ],
    "date-time": "2025-07-12T01:10:19Z",
    "timestamp": 1752282619355,
    "version": "3.32.0"
  },
  "reference-count": 29,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "46",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2004,
        11,
        16
      ]
    ]
  },
  "abstract": "<jats:p>Cooperativity between transcription factors is critical to gene regulation. Current computational methods do not take adequate account of this salient aspect. To address this issue, we present a computational method based on multivariate adaptive regression splines to correlate the occurrences of transcription factor binding motifs in the promoter DNA and their interactions to the logarithm of the ratio of gene expression levels. This allows us to discover both the individual motifs and synergistic pairs of motifs that are most likely to be functional, and enumerate their relative contributions at any arbitrary time point for which mRNA expression data are available. We present results of simulations and focus specifically on the yeast cell-cycle data. Inclusion of synergistic interactions can increase the prediction accuracy over linear regression to as much as 1.5- to 3.5-fold. Significant motifs and combinations of motifs are appropriately predicted at each stage of the cell cycle. We believe our multivariate adaptive regression splines-based approach will become more significant when applied to higher eukaryotes, especially mammals, where cooperative control of gene regulation is absolutely essential.</jats:p>",
  "DOI": "10.1073/pnas.0407365101",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2004,
        11,
        9
      ]
    ],
    "date-time": "2004-11-09T01:25:16Z",
    "timestamp": 1099963516000
  },
  "page": "16234-16239",
  "update-policy": "https://doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 91,
  "title": "Interacting models of cooperative gene regulation",
  "prefix": "10.1073",
  "volume": "101",
  "author": [
    {
      "given": "Debopriya",
      "family": "Das",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and School of Computational Sciences, George Mason University, 10900 University Boulevard, Manassas, VA 20110"
        }
      ]
    },
    {
      "given": "Nilanjana",
      "family": "Banerjee",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and School of Computational Sciences, George Mason University, 10900 University Boulevard, Manassas, VA 20110"
        }
      ]
    },
    {
      "given": "Michael Q.",
      "family": "Zhang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and School of Computational Sciences, George Mason University, 10900 University Boulevard, Manassas, VA 20110"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2004,
        11,
        8
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01763"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)80893-4"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.9.12.3273"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/84792"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0630591100"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng724"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gkg894"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/bioinformatics/btg480"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/bioinformatics/18.9.1167"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/gb-2003-4-7-r43"
    },
    {
      "key": "e_1_3_2_11_2",
      "first-page": "1",
      "volume": "19",
      "year": "1991",
      "unstructured": "Friedman, J. H. (1991) Ann. Stat. 19, 1-67.",
      "journal-title": "Ann. Stat."
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Hastie T. Tibshirani R. & Friedman J. H. (2001) The Elements of Statistical Learning (Springer New York).",
      "DOI": "10.1007/978-0-387-21606-5"
    },
    {
      "key": "e_1_3_2_13_2",
      "unstructured": "Steinberg D. & Colla P. (1999) MARS: An Introduction (Salford Systems San Diego)."
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature01644"
    },
    {
      "key": "e_1_3_2_15_2",
      "unstructured": "Press W. H. Flannery B. P. Teukolsky S. A. & Vetterling W. T. (1992) Numerical Recipes in C: The Art of Scientific Computing (Cambridge Univ. Press Cambridge U. K.)."
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "crossref",
      "first-page": "289",
      "DOI": "10.1111/j.2517-6161.1995.tb02031.x",
      "volume": "57",
      "year": "1995",
      "unstructured": "Benjamini, Y. & Hochberg, Y. (1995) J. R. Stat. Soc. B 57, 289-300.",
      "journal-title": "J. R. Stat. Soc. B"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1097-2765(00)80114-8"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(01)00494-9"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.10.10.3301"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.16.6.2830"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35017581"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.1034302"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.22.2.430-441.2002"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gr.9.11.1040"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/165.3.1017"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gr.301202"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1995.tb00270.x"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gkg200"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gr.1271603"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0407365101",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        12,
        19
      ]
    ],
    "date-time": "2024-12-19T20:57:41Z",
    "timestamp": 1734641861000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0407365101"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2004,
        11,
        8
      ]
    ]
  },
  "references-count": 29,
  "journal-issue": {
    "issue": "46",
    "published-print": {
      "date-parts": [
        [
          2004,
          11,
          16
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0407365101"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0407365101",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2004,
        11,
        8
      ]
    ]
  },
  "assertion": [
    {
      "value": "2004-06-23",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2004-11-08",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}