The digital code of DNA

Hood, Leroy; Galas, David J.

doi:10.1038/nature01410

Cited by 234 publications

(134 citation statements)

References 20 publications

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“…They are given the status of precisely definable 'digital cores of information' that drive the interactions constituting systems. (54,26,33) From the systems-theoretic perspective, the demotion of the genome goes further. Genomes in this framework do not explain anything: they 'merely' comprise some of the components on which higher-level system properties depend.…”

Section: Genomes-in-systemsmentioning

confidence: 99%

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Fundamental issues in systems biology

O’Malley¹,

Dupré²

2005

BioEssays

179

104

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FUNDAMENTAL ISSUES IN SYSTEMS BIOLOGY SummaryIn the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology.Systems biology is best understood as consisting of two streams. One, which we shall call 'pragmatic systems biology', emphasizes large-scale molecular interactions; the other, which we shall refer to as 'systems-theoretic biology', emphasizes system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems and how causality operates at different levels of organization. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realization. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers. KeywordsGenomics, systems biology, systems theory, philosophy of biology 3 FUNDAMENTAL ISSUES IN SYSTEMS BIOLOGYAs genomics matures from a data-collecting enterprise to an explanatory science, and as those scientific endeavours take on disciplinary contours, a range of underlying issues are being explicitly and implicitly addressed by the scientists involved. These reflections are an important part of the way a discipline constitutes itself as a field by setting out central problems and achievements alongside a history of conceptual and empirical precursors. One of the most widely discussed fields in emergent genomics is systems biology, and it raises several important questions that need to be resolved if the science is to advance.The issues that are most fundamental are how the systems that are the focus of systems biology are defined, and how those definitions affect the research agendas that arise from earlier scientific legacies. Preceding interpretations of genomicsThe early days of genomics began with fairly simple conceptualizations that emphasized the shift from identifying genes to sequencing and mapping entire genomes. (1) As the data poured in and the field achieved wide recognition, these definitions were expanded to give greater emphasis to functional analyses. (2,3) Although much of the discussion of the status of genomes has been conducted via evaluations of the evolving metaphors in genomic discourse -from the ineptness of the blueprint metaphor to analogies with jazz scores and Theseus's 4 ship - (4,5,6) there are also some excellent systematic discussions of genome conceptualizations. (7) Two issues concerning the status of knowledge in genomics are frequently discussed. The first is that early genomics shared the reductionist aspirations of genetics, which led to a preoccupation with sequence structure and deterministic accounts of function. (3, 8) Persistent (and prescient) demands for a more hierarchical and less simplistically deterministic understanding of molecular processes were voiced even in the early years of genomics. (9,10) These calls increased with ...

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Section: Genomes-in-systemsmentioning

confidence: 99%

“…(12,26,29,40,54,62,58) The common theme of all outlines of systems biology is integration, hence systems biology's other moniker of 'integrative biology'. (70,71) None of this discussion, however, goes much beyond endorsing such fusions.…”

Section: Integration Of Approachesmentioning

confidence: 99%

Fundamental issues in systems biology

O’Malley¹,

Dupré²

2005

BioEssays

179

104

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“…1 A variety of DNA detection formats are now available, including both heterogeneous assays with surface-bound array-based probes and homogeneous solution-based detection schemes. 2 A number of those rely on fluorescence signal and, in particular, on fluorescence (or Fö rster) resonant energy transfer (FRET).…”

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confidence: 99%

Cascaded FRET in Conjugated Polymer/Quantum Dot/Dye-Labeled DNA Complexes for DNA Hybridization Detection

et al. 2009

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A s the human genome project has uncovered the full sequence of human genomes and the postgenome technologies have been rapidly developed, DNA hybridization detection has become increasingly important. 1 A variety of DNA detection formats are now available, including both heterogeneous assays with surface-bound array-based probes and homogeneous solution-based detection schemes. 2 A number of those rely on fluorescence signal and, in particular, on fluorescence (or Fö rster) resonant energy transfer (FRET). 3 Both conjugated polymers and semiconductor nanocrystals (colloidal quantum dots, QDs) have been suggested for use as fluorescent entities in DNA detection assays. 4Ϫ12 Assays based on watersoluble cationic conjugated polymers allow one to utilize a simple binding strategy to DNA through electrostatic interactions with ionic side groups and benefit from the lightharvesting properties along the polymer backbone. 4Ϫ8 QDs have been increasingly used as donors in FRET-related studies, including optical DNA diagnostics. 9Ϫ12 QDs are photostable, highly efficient fluorophores with a strong band gap luminescence tunable by size as a result of the quantum confinement effect. 13 FRET in QD/ DNA/organic dye conjugates has been used to study DNA hybridization, 14,15 cleavage, 16 and replication. 17 Most of the reported approaches required covalent conjugation of DNA to the QD surface (e.g., by EDC/NHS coupling reaction), which often decreases the colloidal stability and/or the emission intensity of QDs. 18,19 This limitation can be overcome by the use of a sensing platform relying on the electrostatic interaction of dye-labeled DNA with the oppositely charged QD surface 20 in a similar fashion as in conducting polymer-based detection assays. 4Ϫ8 In this paper, we propose a simultaneous use of conjugated polymers and semiconductor QDs for DNA hybridization detection, which can potentially combine advantages of both light-harvesting and DNA-binding properties of water-soluble polymers with photostability, lightharvesting ability, and FRET donor property of QDs. A blue-emitting conjugated polymer with positively charged side chains electrostatically self-assembles on the negatively charged surface of red-emitting CdTe QDs. The so-formed hybrid complex has a net positive charge and thus attracts negatively charged dye-labeled DNA molecules (Scheme 1). The water-soluble, cationic, conjugated polymer, poly[9,9-bis(3=-((N,N-

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“…I n jawed vertebrates, the adaptive immune system is characterized by the exponential diversity of its Ag receptors (1)(2)(3)(4)(5). In contrast to the receptors of the innate immune system that bind relatively invariant pathogen-associated epitopes (6), diverse Ag receptor repertoires allow recognition of novel or divergent epitopes on pathogens or toxins.…”

mentioning

confidence: 99%

Development of the Expressed Ig CDR-H3 Repertoire Is Marked by Focusing of Constraints in Length, Amino Acid Use, and Charge That Are First Established in Early B Cell Progenitors

Ivanov

Schelonka

Zhuang

et al. 2005

The Journal of Immunology

200

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To gain insight into the mechanisms that regulate the development of the H chain CDR3 (CDR-H3), we used the scheme of Hardy to sort mouse bone marrow B lineage cells into progenitor, immature, and mature B cell fractions, and then performed sequence analysis on VH7183-containing Cμ transcripts. The essential architecture of the CDR-H3 repertoire observed in the mature B cell fraction F was already established in the early pre-B cell fraction C. These architectural features include VH gene segment use preference, DH family usage, JH rank order, predicted structures of the CDR-H3 base and loop, and the amino acid composition and average hydrophobicity of the CDR-H3 loop. With development, the repertoire was focused by eliminating outliers to what appears to be a preferred repertoire in terms of length, amino acid composition, and average hydrophobicity. Unlike humans, the average length of CDR-H3 increased during development. The majority of this increase came from enhanced preservation of JH sequence. This was associated with an increase in the prevalence of tyrosine. With an accompanying increase in glycine, a shift in hydrophobicity was observed in the CDR-H3 loop from near neutral in fraction C (−0.08 ± 0.03) to mild hydrophilic in fraction F (−0.17 ± 0.02). Fundamental constraints on the sequence and structure of CDR-H3 are thus established before surface IgM expression.

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The digital code of DNA

Cited by 234 publications

References 20 publications

Fundamental issues in systems biology

Fundamental issues in systems biology

Cascaded FRET in Conjugated Polymer/Quantum Dot/Dye-Labeled DNA Complexes for DNA Hybridization Detection

Development of the Expressed Ig CDR-H3 Repertoire Is Marked by Focusing of Constraints in Length, Amino Acid Use, and Charge That Are First Established in Early B Cell Progenitors

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