Search arXiv⌕ Search

arXiv · 0709.3156

Two distinct logical types of network control in gene expression profiles

Abstract

In unicellular organisms such as bacteria the same acquired mutations beneficial in one environment can be restrictive in another. However, evolving Escherichia coli populations demonstrate remarkable flexibility in adaptation. The mechanisms sustaining genetic flexibility remain unclear. In E. coli the transcriptional regulation of gene expression involves both dedicated regulators binding specific DNA sites with high affinity and also global regulators - abundant DNA architectural proteins of the bacterial chromoid binding multiple low affinity sites and thus modulating the superhelical density of DNA. The first form of transcriptional regulation is dominantly pairwise and specific, representing digitial control, while the second form is (in strength and distribution) continuous, representing analog control. Here we look at the properties of effective networks derived from significant gene expression changes under variation of the two forms of control and find that upon limitations of one type of control (caused e.g. by mutation of a global DNA architectural factor) the other type can compensate for compromised regulation. Mutations of global regulators significantly enhance the digital control; in the presence of global DNA architectural proteins regulation is mostly of the analog type, coupling spatially neighboring genomic loci; together our data suggest that two logically distinct types of control are balancing each other. By revealing two distinct logical types of control, our approach provides basic insights into both the organizational principles of transcriptional regulation and the mechanisms buffering genetic flexibility. We anticipate that the general concept of distinguishing logical types of control will apply to many complex biological networks.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Carsten Marr, Marcel Geertz, Marc-Thorsten Huett, Georgi Muskhelishvili. 2007-09-20. Two distinct logical types of network control in gene expression profiles. https://arxiv.org/abs/0709.3156

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

EMMA: an R/Bioconductor package to automate tracking of metadata in functional enrichment analyses

Summary: Functional enrichment analysis (FEA) is a widely used approach for interpreting high-throughput omics data. However, essential methodological details, such as software versions, analysis parameters, and annotation database releases among others, are often incompletely reported, limiting the reproducibility and transparency of enrichment analyses and complicating the assessment of potentially problematic methodological choices. Here we present EMMA, an R/Bioconductor package that integrates with existing FEA tools and automatically captures provenance metadata, such as annotation metadata, software version, and parameters, during the analysis runtime. Our package provides utilities for accessing and exporting the recorded metadata to facilitate transparent reporting and preserve provenance required for reproducible enrichment analyses. This also enables auditing of the results while remaining compatible with existing Bioconductor workflows. Availability and implementation: EMMA is available on Bioconductor under the MIT license (https: //bioconductor.org/packages/EMMA), with its development version also available on GitHub (https: //github.com/imbeimainz/EMMA).

q-bio.GN↗

Motif-Vocab: StatisticallyCalibrated Transcription-Factor-Identity Tokenization forGenomic Language Models

Tokenization is a central design choice in genomic language models, yet most deoxyribonucleic acid (DNA) tokenizers use characters, fixed-length k-mers, or frequency-derived subwords without explicitly using prior information about the specificity of DNA-binding regulatory factors. We introduce Motif-Vocab, a biologically informed tokenizer that scans both DNA strands for statistically calibrated motif matches, emits transcription-factor (TF) identity tokens, and applies nucleotide, $k$-mer, or byte-pair encoding (BPE) to unmatched sequence. Motif-specific null distributions put position-weight matrices (PWMs) of different lengths and degeneracy on a common significance scale; deterministic overlap rules make the representation reproducible. In controlled Bidirectional Encoder Representations from Transformers (BERT) pretraining on two billion base pairs, real motif libraries outperform randomized-motif controls on 54 of 55 in-scope downstream tasks. On a motif-disjoint recognition task derived from DART-Eval Task 2, TF-specific tokens improve macro-F1 by 0.040 over a position-matched generic motif token and by 0.033 over a matched no-motif tokenizer (95\% bootstrap confidence interval: 0.027--0.038). Motif tokens also receive stronger attribution and produce larger occlusion effects than shuffled controls. Dense no-motif tokenizers remain strong general-purpose baselines, including a near-tie on the five-task BERT-base panel. Thus, Motif-Vocab is not a universal accuracy replacement; it is a targeted, interpretable inductive bias for motif-sensitive genomic modeling.

q-bio.GN↗

Revolutionizing Genomics with Reinforcement Learning Techniques

In recent years, Reinforcement Learning (RL) has emerged as a powerful tool for solving a wide range of problems, including decision-making and genomics. The exponential growth of raw genomic data over the past two decades has exceeded the capacity of manual analysis, leading to a growing interest in automatic data analysis and processing. RL algorithms are capable of learning from experience with minimal human supervision, making them well-suited for genomic data analysis and interpretation. One of the key benefits of using RL is the reduced cost associated with collecting labeled training data, which is required for supervised learning. While there have been numerous studies examining the applications of Machine Learning (ML) in genomics, this survey focuses exclusively on the use of RL in various genomics research fields, including gene regulatory networks (GRNs), genome assembly, and sequence alignment. We present a comprehensive technical overview of existing studies on the application of RL in genomics, highlighting the strengths and limitations of these approaches. We then discuss potential research directions that are worthy of future exploration, including the development of more sophisticated reward functions as RL heavily depends on the accuracy of the reward function, the integration of RL with other machine learning techniques, and the application of RL to new and emerging areas in genomics research. Finally, we present our findings and conclude by summarizing the current state of the field and the future outlook for RL in genomics.

q-bio.GN↗