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Results for “molecular biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 19 recordsLinked to original sources

bioRxiv2026

BioTrouble: A Multi-Agent Workflow for Troubleshooting Molecular Biology Techniques

Troubleshooting is a critical yet often underdocumented aspect of molecular biology experiments across laboratories. Failures in core techniques such as PCR, qPCR, molecular cloning, and related assays can lead to experimental failure, wasted resources, and delays in research progress. Here, we present BioTrouble, a multi-agent AI workflow designed to assist researchers in troubleshooting a wide range of molecular biology experiments. It leverages a custom-designed troubleshooting knowledge base through a retrieval-augmented generation (RAG) framework. BioTrouble employs small language models to generate the troubleshooting plan and utilizes a smart model routing system to manage cost per request. User interactions and feedback are stored as structured cases, enabling BioTrouble to expand its troubleshooting knowledge base and improve response generation over time. Compared with single-model SOTA LLM, BioTrouble generated comparable troubleshooting recommendations using small language models.

bioinformatics↗

bioRxiv2024

Parallel maximal common subgraphs with labels for molecular biology

Advances in graph algorithmics have allowed in-depth study of many natural objects from molecular biology or chemistry to social networks. Particularly in molecular biology and cheminformatics, understanding complex structures by identifying conserved sub-structures is a key milestone towards the artificial design of novel components with specific functions. Given a dataset of structures, we are interested in identifying all maximum common connected partial subgraphs between each pair of graphs, a task notoriously NP-Hard. In this work, we present parallel algorithms over shared and distributed memory to enumerate all maximal connected common sub-graphs between pairs of arbitrary multi-directed graphs with labels on their edges. We offer an implementation of these methods and evaluate their performance on the non-redundant dataset of all known RNA 3D structures. We show that we can compute the exact results in a reasonable time for each pairwise comparison while taking into account a much more diverse set of interactions--resulting in much denser graphs--resulting in an order of magnitude more conserved modules. All code is available at https://gitlab.info.uqam.ca/cbe/pasigraph and results in the branch results.

bioinformatics↗

bioRxiv2023

An effective C. elegans CRISPR training module for high school and undergraduate summer research experiences in molecular biology

Engaging in research experiences as a high school or undergraduate student interested in science, technology, engineering, and mathematics (STEM) is pivotal for their academic and professional development. A structured teaching framework can help cultivate a students curiosity and passion for learning and research. In this study, an effective eight-week training program has been created that encompasses fundamental molecular biology principles and hands-on laboratory activities. This curriculum focuses on using clustered regularly interspaced short palindromic repeats (CRISPR) gene editing in the Caenorhabditis elegans model organism. Through pre- and post-program assessments, substantial enhancements in students molecular biology proficiency and enthusiasm for scientific exploration was observed. Overall, this diligently crafted training module that employs C. elegans as an educational tool to instruct inexperienced students has demonstrated its accessibility and ability to engage students in molecular biology and gene editing methodologies.

scientific communication and education↗

bioRxiv2017

The evolution of central dogma of molecular biology: a logic-based dynamic approach

It is nearly half a century past the age of the introduction of the Central Dogma (CD) of molecular biology. This biological axiom has been developed and currently appears to be all the more complex. In this study, we modified CD by adding further species to the CD information flow and mathematically expressed CD within a dynamic framework by using Boolean network based on its present-day and 1965 editions. We show that the enhancement of the Dogma not only now entails a higher level of complexity, but it also shows a higher level of robustness, thus far more consistent with the nature of biological systems. Using this mathematical modeling approach, we put forward a logic-based expression of our conceptual view of molecular biology. Finally, we show that such biological concepts can be converted into dynamic mathematical models using a logic-based approach and thus may be useful as a framework for improving static conceptual models in biology.

systems biology↗

bioRxiv2024

Open Educational Resources for distributed hands-on teaching in molecular biology

The urgent need to develop a more equitable bioeconomy has positioned biotechnology capacity building at the forefront of international priorities. However, in many educational institutions, particularly in low-and middle-income countries, this remains a major challenge due to limited access to reagents, equipment, and technical documentation. In this work, we describe Open Educational Resources (OER) composed of locally produced biological reagents, open source hardware and free software to teach fundamental techniques in biotechnology such as LAMP DNA amplification, RT-PCR RNA detection, enzyme kinetics and fluorescence imaging. The use of locally produced reagents and devices reduces costs by up to one order of magnitude. During the pandemic lockdowns, these tools were distributed nationwide to students homes as a lab-in-a-box for remote teaching of molecular biology. To test their performance, a total of 93 undergraduate students tested these resources during a biochemistry practical course. 27 out of 31 groups ([~]87%) successfully achieved the objectives of the PCR activity, while 28 out of 31 groups ([~]90%) correctly identified the target using LAMP reactions. To assess the potential application in secondary school, we organized three workshops for high school teachers from different institutions across Chile and performed an anonymous questionnaire, obtaining a strong agreement on how these OER broaden teachers perspectives on the techniques and facilitate the teaching of molecular biology topics. This effort was made possible through a close collaboration with open source technology advocates and members of DIYbio communities, whose work is paving the way for low-cost training in biology. All the protocols and design files are available under open source licenses.

molecular biology↗

bioRxiv2018

25 Years of Molecular Biology Databases: A Study of Proliferation, Impact, and Maintenance

Online resources enable unfettered access to and analysis of scientific data and are considered crucial for the advancement of modern science. Despite the clear power of online data resources, including web-available databases, proliferation can be problematic due to challenges in sustainability and long-term persistence. As areas of research become increasingly dependent on access to collections of data, an understanding of the scientific communitys capacity to develop and maintain such resources is needed.\n\nThe advent of the Internet coincided with expanding adoption of database technologies in the early 1990s, and the molecular biology community was at the forefront of using online databases to broadly disseminate data. The journal Nucleic Acids Research has long published articles dedicated to the description of online databases, as either debut or update articles. Snapshots throughout the entire history of online databases can be found in the pages of Nucleic Acids Research s \"Database Issue.\" Given the prominence of the Database Issue in the molecular biology and bioinformatics communities and the relative rarity of consistent historical documentation, database articles published in Database Issues provide a particularly unique opportunity for longitudinal analysis.\n\nTo take advantage of this opportunity, the study presented here first identifies each unique database described in 3055 Nucleic Acids Research Database Issue articles published between 1991-2016 to gather a rich dataset of databases debuted during this time frame, regardless of current availability. In total, 1727 unique databases were identified and associated descriptive statistics were gathered for each, including year debuted in a Database Issue and the number of all associated Database Issue publications and accompanying citation counts. Additionally, each database identified was assessed for current availability through testing of all associated URLs published. Finally, to assess maintenance, database websites were inspected to determine the last recorded update. The resulting work allows for an examination of the overall historical trends, such as the rate of database proliferation and attrition as well as an evaluation of citation metrics and on-going database maintenance.

molecular biology↗

bioRxiv2025

A Versatile, Simple, and Rapid (VSR) method for generating gene clones, diverse mutants, and short gene fragments for molecular biology applications

Gene cloning, site-directed mutagenesis (SDM), and short gene synthesis are essential tools in molecular biology, yet existing approaches remain constrained by efficiency, flexibility, and cost. Here, we developed a versatile, simple, and rapid (VSR) 3-in-1 method that integrates seamless cloning, mutagenesis, and short gene assembly in a single platform. This approach works on the principles of overlap extension polymerase chain reaction (OPCR), uses high-fidelity DNA polymerase and short overlapping primers. Target genes can be directly amplified from genomic DNA or complementary DNA (cDNA) templates and cloned into vectors without intermediate purification, restriction enzyme digestion, or ligation. VSR supports the insertion of DNA fragments ranging from 80 bp to 33 kb at any plasmid locus while enabling the introduction of single or multiple nucleotide substitutions at one or more sites in a single reaction. Using this method, we cloned 35 genes of diverse lengths and two complete viral genomes with efficiencies ranging from 60-100% and introduced up to 17 substitutions in a single mutagenesis reaction. We further demonstrate efficient de novo synthesis of short genes from overlapping oligonucleotides. The VSR method is a reliable, rapid, and cost-effective approach with a wide range of applications for both routine and high-throughput workflows. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/682745v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1295a5aorg.highwire.dtl.DTLVardef@1eacb4eorg.highwire.dtl.DTLVardef@1c98fb1org.highwire.dtl.DTLVardef@1f8bcbe_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

What Large Language Models Know About Plant Molecular Biology

Large language models (LLMs) are rapidly permeating scientific research, yet their capabilities in plant molecular biology remain largely uncharacterized. Here, we present MOBIPLANT, the first comprehensive benchmark for evaluating LLMs in this domain, developed by a consortium of 112 plant scientists across 19 countries. MOBIPLANT comprises 565 expert-curated multiple-choice questions and 1,075 synthetically generated questions, spanning core topics from gene regulation to plant-environment interactions. We benchmarked seven leading chat-based LLMs using both automated scoring and human evaluation of open-ended answers. Models performed well on multiple-choice tasks (exceeding 75% accuracy), although most of them exhibited a consistent bias towards option A. In contrast, expert reviews exposed persistent limitations, including factual misalignment, hallucinations, and low self-awareness. Critically, we found that model performance strongly correlated with the citation frequency of source literature, suggesting that LLM knowledge inherits the visibility distribution of the underlying scientific corpus. Consequently, models tend to be more reliable on consolidated topics and less reliable on under-cited or recently emerging ones. We also benchmarked agents equipped with web-search and additional tools in more complex tasks involving DNA sequence analysis. These agents were outperformed by domain specific models in sequence classification and regression tasks, indicating an opportunity for joint agentic systems that combine both the reasoning power of LLMs and the dedicated processing of DNA models. This understanding is key to guiding both the development of next-generation models and the informed use of current tools in the everyday work of plant researchers. MOBIPLANT is publicly available online in this link.

plant biology↗

bioRxiv2018

Evaluating Named-Entity Recognition approaches in plant molecular biology

Text mining research is becoming an important topic in biology with the aim to extract biological entities from scientific papers in order to extend the biological knowledge. However, few thorough studies on text mining and applications are developed for plant molecular biology data, especially rice, thus resulting a lack of datasets available to train models able to detect entities such as genes, proteins and phenotypic traits. Since there is rare benchmarks for rice, we have to face various difficulties in exploiting advanced machine learning methods for accurate analysis of rice bibliography. In this article, we developed a new training datasets (Oryzabase) as the benchmark. Then, we evaluated the performance of several current approaches to find a methodology with the best results and assigned it as the state of the art method for our own technique in the future. We applied Name Entities Recognition (NER) tagger, which is built from a Long Short Term Memory (LSTM) model, and combined with Conditional Random Fields (CRFs) to extract information of rice genes and proteins. We analyzed the performance of LSTM-CRF when applying to the Oryzabase dataset and improved the results up to 86% in F1. We found that on average, the result from LSTM-CRF is more exploitable with the new benchmark.

bioinformatics↗

bioRxiv2019

Homeostasis in the Central Dogma of Molecular Biology

Cell survival requires the control of biomolecule concentration, i.e. biomolecules should approach homeostasis. With information-carrying macromolecules, the particular concentration variation ranges depend on each type: DNA is not buffered, but mRNA and protein concentrations are homeostatically controlled, which leads to the ribostasis and proteostasis concepts. In recent years, we have studied the particular features of mRNA ribostasis and proteostasis in the model organism S. cerevisiae. Here we extend this study by comparing published data from three other model organisms: E. coli, S. pombe and cultured human cells. We describe how mRNA ribostasis is less strict than proteostasis. A constant ratio appears between the average decay and dilution rates during cell growth for mRNA, but not for proteins. We postulate that this is due to a trade-off between the cost of synthesis and the response capacity. This compromise takes place at the transcription level, but is not possible at the translation level as the high stability of proteins, versus that of mRNAs, precludes it. We hypothesize that the middle-place role of mRNA in the Central Dogma of Molecular Biology and its chemical instability make it more suitable than proteins for the fast changes needed for gene regulation.\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=147 SRC=\"FIGDIR/small/599050v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (24K):\norg.highwire.dtl.DTLVardef@95419aorg.highwire.dtl.DTLVardef@10612e5org.highwire.dtl.DTLVardef@1c29081org.highwire.dtl.DTLVardef@9d21c0_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

molecular biology↗

bioRxiv2017

IntelliEppi: Intelligent reaction monitoring and holistic data management system for the molecular biology lab

Daily alterations of routines and protocols create high, yet so far unmet demands for intelligent reaction monitoring, quality control and data management in molecular biology laboratories. To meet such needs, the \"internet of things\" is implemented here. We propose an approach which combines direct tracking of lab tubes, reactions and racks with a comprehensive data management system. Reagent tubes in this system are tagged with 2D data matrices or imprinted RFID-chips using a unique identification number. For each tube, individual content and all relevant information based on conducted experimental procedures are stored in an experimental data management system. This information is managed automatically but allow scientists to engage and interfere via user-friendly graphical interface. Tagged tubes are used in connection with a detectable RFID-tagged rack. We show that reaction protocols, HTS storage and complex reactions are easily planned and controlled.

bioinformatics↗

bioRxiv2025

Chromatin profiling for everyone: FFPE-CUTAC for the theory and practice of modern molecular biology

In 2025, together with the Fred Hutch Summer Undergraduate Research and Summer High School Internship programs, we developed and implemented a laboratory genomics research experience to introduce students to modern molecular biology techniques and bioinformatics. The course centered around using a new method we had developed in 2023 that uses readily available fixed tissue sections on glass slides. Students performed a series of steps to tagment genomic locations of RNA Polymerase II and then used PCR to enrich libraries for next-generation sequencing in a core facility. Students then visualized their data in genomic browser tracks and assessed the results. At the end of the summer, students prepared and presented their work and experiences in seminar format to their cohorts. Overall, the technical simplicity of on-slide chromatin profiling introduced the students to laboratory practice and current techniques in genomics, bioinformatics, and medical sciences.

scientific communication and education↗

bioRxiv2019

Who Bears the Burden of Long-Lived Molecular Biology Databases?

In the early 1990s the life sciences quickly adopted online databases to facilitate wide-spread dissemination and use of scientific data. From 1991, the journal Nucleic Acids Research has published an annual Database Issue dedicated to articles describing molecular biology databases. Analysis of these articles reveals a set of long-lived databases which have now remained available for more than 15 years. Given the pervasive challenge of sustaining community resources, these databases provide an opportunity to examine what factors contribute to persistence by addressing two questions 1) which organizations fund these long-lived databases? and 2) which organizations maintain these long-lived databases? Funding and operating organizations for 67 databases were determined through review of Database Issue articles. The results reveal a diverse set of contributing organizations with financial and operational support spread across six categories: academic, consortium/collective, government, industry, philanthropic, and society/association. The majority of databases reported support from more than one funding organization, of which government organizations were most common source of funds. Operational responsibilities were more distributed, with academic organizations serving as the most common hosts. Although overall there is evidence of diversification, the most acknowledged funding and operating organizations contribute to disproportionately large percentages of the long-lived databases investigated here.

scientific communication and education↗

bioRxiv2019

Molecular Biology Information Service: An innovative medical library-based bioinformatics support service for biomedical researchers

Biomedical researchers are increasingly reliant on obtaining bioinformatics training in order to conduct their research. Here we present a model that academic institutions may follow to provide such training for their researchers, based on the Molecular Biology Information Service (MBIS) of the Health Sciences Library System, University of Pittsburgh. The MBIS runs a four-facet service with the following goals: (1) identify, procure, and implement commercially-licensed bioinformatics software, (2) teach hands-on workshops using bioinformatics tools to solve research questions, (3) provide in-person and email consultations on software/databases, and (4) maintain a web portal providing overall guidance on the access and use of bioinformatics resources and MBIS-created webtools. This paper describes these facets of MBIS activities from 2006-2018, including outcomes from a survey measuring attitudes of University of Pittsburgh researchers about MBIS service and performance.

bioinformatics↗

bioRxiv2021

Biological, Molecular And Phiysiological Characterization Of Four Soybean mosaic virus Isolates Present In Argentine Soybean Crops

Soybean mosaic virus (SMV) causes systemic infections in soybean plants, leading to chlorotic mosaic and producing significant yield losses. The virus is widely distributed in all soybean production areas in the world. In Argentina, three geographical isolates were identified: Marcos Juarez (MJ), Manfredi (M), and North Western Argentina (NOA), and another isolate named "Planta Vinosa" (PV), which causes severe necrosis symptoms in some cultivars. Here, the biological, molecular and physiological characterization of these isolates was performed for the first time. Three of the four isolates showed a low genetic divergence in the evaluated genes (P1, CI and CP). Although SMV-NOA and SMV-PV had high homology at the sequence level, they showed wide differences in pathogenicity, seed mottling and the ability of transmission by seeds or aphids, as well as in physiological effects. SMV-NOA caused early alterations (before symptom appearance, BS) in {Phi}PSII and MDA content in leaves with respect to the other isolates. After the appearance of macroscopic symptoms (late symptoms, LS), SMV-M caused a significant increase in the content of MDA, total soluble sugars, and starch with respect to the other isolates. Thus, early alterations of {Phi}PSII and soluble sugars might have an impact on late viral symptoms. Likewise, SMV-MJ developed more severe symptoms in the susceptible Davis cultivar than in DM 4800. Therefore, our results show differences in genome, biological properties and physiological effects among SMV isolates as well as different interactions of SMV-MJ with two soybean cultivars.

plant biology↗

bioRxiv2020

Towards XNA molecular biology: Bacterial cell display as a robust and versatile platform for the engineering of low affinity ligands and enzymes

Although directed evolution has been remarkably successful at expanding the chemical and functional boundaries of biology, it is limited by the robustness and flexibility of available selection platforms - traditionally designed around a single desired function with limited scope for alternative applications. We report SNAP as a quantitative reporter for bacterial cell display, which enabled fast troubleshooting and systematic development of the selection platform. In addition, we demonstrate that even weak interactions between displayed proteins and nucleic acids can be harnessed towards specific labelling of bacterial cells, allowing functional characterisation of DNA binding proteins and enzymes. Together, this establishes bacterial display as a viable route towards the systematic engineering of all ligands and enzymes required for the development of XNA molecular biology.

synthetic biology↗

bioRxiv2019

Robustness and lethality in multilayer biological molecular networks

Robustness is a prominent feature of most biological systems. In a cell, the structure of the interactions between genes, proteins, and metabolites has a crucial role in maintaining the cells functionality and viability in presence of external perturbations and noise. Despite advances in characterizing the robustness of biological systems, most of the current efforts have been focused on studying homogeneous molecular networks in isolation, such as protein-protein or gene regulatory networks, neglecting the interactions among different molecular substrates. Here we propose a comprehensive framework for understanding how the interactions between genes, proteins and metabolites contribute to the determinants of robustness in a heterogeneous biological network. We integrate heterogeneous sources of data to construct a multilayer interaction network composed of a gene regulatory layer, and protein-protein interaction layer and a metabolic layer. We design a simulated perturbation process to characterize the contribution of each gene to the overall systems robustness, defined as its influence over the global network. We find that highly influential genes are enriched in essential and cancer genes, confirming the central role of these genes in critical cellular processes. Further, we determine that the metabolic layer is more vulnerable to perturbations involving genes associated to metabolic diseases. By comparing the robustness of the network to multiple randomized network models, we find that the real network is comparably or more robust than expected in the random realizations. Finally, we analytically derive the expected robustness of multilayer biological networks starting from the degree distributions within or between layers. These results provide new insights into the non-trivial dynamics occurring in the cell after a genetic perturbation is applied, confirming the importance of including the coupling between different layers of interaction in models of complex biological systems.

systems biology↗

bioRxiv2017

On a non-trivial application of Algebraic Topology to Molecular Biology

Brouwers fixed point theorem, a fundamental theorem in algebraic topology proved more than a hundred years ago, states that given any continuous map from a closed, simply connected set into itself, there is a point that is mapped unto itself. Here we point out the connection between a one-dimensional application of Brouwers fixed point theorem and a mechanism proposed to explain how extension of single-stranded DNA substrates by recombinases of the RecA superfamily facilitates significantly the search for homologous sequences on long chromosomes.

molecular biology↗