
Natalio KrasnogorNewcastle University | NCL · School of Computing Science
Natalio Krasnogor
Analista de Computacion, Licenciado Informatica, PhD
About
306
Publications
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Introduction
My research activities lie at the interface of Computing Science and the Natural Sciences, e.g. Biology, Chemistry and Physics. I apply my expertise on Machine Intelligence (e.g. optimisation, data mining, big data, evolutionary learning), Complex Systems and Unconventional Computing (e.g. biocomputing) to Bioinformatics, Systems and Synthetic Biology
Publications
Publications (306)
DNA origami is a mainstay of DNA nanotechnology and several efforts have been devoted to understanding how various factors of the self-assembly reaction affect the final yield of the target origami structure. This study analyses how base sequence affects origami yield through the generation of off-target side reactions during selfassembly. Off-targ...
This is Supplementary Information to the paper below.
Designs for scaffolded DNA origami nanostructures are commonly and minimally published as the list of DNA staple and scaffold sequences required. In nearly all cases, high-level editable design files (e.g. caDNAno) which generated the low-level sequences are not made available. This de facto ‘raw sequence’ exchange format allows published origami d...
The formalization of biological systems using computational modelling approaches as an alternative to mathematical-based methods has recently received much interest because computational models provide a deeper mechanistic understanding of biological systems. In particular, formal verification, complementary approach to standard computational techn...
Designs for scaffolded DNA origami nanostructures are commonly and minimally published as the list of DNA staple and scaffold sequences required. In nearly all cases, high-level editable design files (e.g. caDNAno) which generated the low-level sequences are not made available. This de facto 'raw sequence' exchange format allows published origami d...
Binary light-up aptamers are intriguing and emerging tools with potential in different fields. Herein, we demonstrate the versatility of a split Broccoli aptamer system able to turn on the fluorescence signal only in the presence of a complementary sequence.
First, an RNA three-way junction harbouring the split system was assembled in an E. coli ba...
“Full-stack” biotechnology platforms for cell line (re)programming are on the horizon, thanks mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration of life science research with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption...
Cell-cell adhesion between oral bacteria plays a key role in the development of polymicrobial communities such as dental plaque. Oral streptococci such as Streptococcus gordonii and Streptococcus oralis are important early colonizers of dental plaque and bind to a wide range of different oral microorganisms, forming multispecies clumps or ‘coaggreg...
Genome editing methods based on group II introns (known as targetron technology) have long been used as a gene knockout strategy in a wide range of organisms, in a fashion independent of homologous recombination. Yet, their utility as delivery systems has typically been suboptimal due to the reduced efficiency of insertion when carrying exogenous s...
DNA-based memory systems are being reported with increasing frequency. However, dynamic DNA data structures able to store and recall information in an ordered way, and able to be interfaced with external nucleic acid computing circuits, have so far received little attention. Here we present an in vitro implementation of a stack data structure using...
We present the Infobiotics Workbench (IBW), a user-friendly, scalable, and integrated computational environment for the computer-aided design of synthetic biological systems. It supports an iterative workflow that begins with specification of the desired synthetic system, followed by simulation and verification of the system in high-performance env...
Genome editing methods based on Group II introns (known as Targetron technology) have been long used as a gene knock-out strategy in a wide range of organisms in a fashion independent of homologous recombination. Yet, their utility as delivery systems has been typically suboptimal because of their reduced efficiency of insertion when they carry exo...
“Full-stack” biotechnology platforms for cell line (re)programming are on the horizon, due mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption of biological products. Hen...
The success of any machine learning technique depends on the correct setting of its parameters and, when it comes to large-scale datasets, hand-tuning these parameters becomes impractical. However, very large-datasets can be pre-processed in order to distil information that could help in appropriately setting various systems parameters. In turn, th...
The scaffolded origami technique is an attractive tool for engineering nucleic acid nanostructures. This paper demonstrates scaffolded RNA origami folding in vitro in which, for the first time, all components are transcribed simultaneously in a single-pot reaction. Double-stranded DNA sequences are transcribed by T7 RNA polymerase into scaffold and...
As DNA sequencing and synthesis become cheaper and more easily accessible, the scale and complexity of biological engineering projects is set to grow. Yet, although there is an accelerating convergence between biotechnology and digital technology, a deficit in software and laboratory techniques diminishes the ability to make biotechnology more agil...
β-cell dysfunction in type 2 diabetes (T2D) is associated with loss of cellular identity and mis-expression of alternative islet hormones, including glucagon. The molecular basis for these cellular changes has been attributed to dysregulation of core β-cell transcription factors, which regulate β-cell identity through activating and repressive mech...
The scaffolded origami technique has provided an attractive tool for engineering nucleic acid nanostructures. This paper demonstrates scaffolded RNA origami folding in vitro in which all components are transcribed simultaneously in a single-pot reaction. Double-stranded DNA sequences are transcribed by T7 RNA polymerase into scaffold and staple str...
Context:
Although diabetes affects 40-50% of adults with cystic fibrosis, remarkably little is known regarding the underlying mechanisms leading to impaired pancreatic β-cell insulin secretion. Efforts towards improving the functional β-cell deficit in cystic fibrosis related diabetes (CFRD) have been hampered by an incomplete understanding of whet...
Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age-related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has...
As DNA sequencing and synthesis become cheaper and more easily accessible, the scale and complexity of biological engineering projects is set to grow. Yet, although there is an accelerating convergence between biotechnology and computing science, a deficit in software and laboratory techniques diminishes the ability to make biotechnology more agile...
Many oral bacteria form macroscopic clumps known as coaggregates when mixed with a different species. It is thought that these cell-cell interactions are critical for the formation of mixed-species biofilms such as dental plaque. Here, we assessed the impact of coaggregation between two key initial colonizers of dental plaque, Streptococcus gordoni...
Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites, which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that...
Motivation:
3D physical modelling is a powerful computational technique that allows for the simulation of complex systems such as consortia of mixed bacterial species. The complexities in physical modelling reside in the knowledge intensive model building process and the computational expense in calculating their numerical solutions. These models...
Cell‐cell interactions between genetically distinct bacteria, known as coaggregation, are important for the formation of mixed‐species biofilms such as dental plaque. Interactions lead to gene regulation in the partner organisms that may be critical for adaptation and survival in mixed‐species biofilms. Here, gene regulation responses to coaggregat...
Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well...
Motivation: 3D physical modelling is a powerful computational technique that allows for the simulation of complex systems such as consortia of mixed bacterial species. The complexities in physical modelling reside in the knowledge intensive model building process and the computational expense in calculating their numerical solutions. These models c...
Autocatalytic sets are self-sustaining and collectively catalytic chemical reaction networks which are believed to have played an important role in the origin of life. Simulation studies have shown that autocatalytic sets are, in principle, evolvable if multiple autocatalytic subsets can exist in different combinations within compartments, i.e., so...
RNA presents intringuing roles in many cellular processes and its versatility underpins many different applications in synthetic biology. Nonetheless, RNA origami as a method for nanofabrication is not yet fully explored and the majority of RNA nanostructures are based on natural pre-folded RNA. Here we describe a biologically inert and uniquely ad...
Statement of significance:
The expression and the role of many extracellular matrix (ECM) components during human retinal development is not fully understood. In this study, expression of key ECM components (Collagen IV, Fibronectin, Brevican, Versican, IMPG1 and IMPG2) was investigated during human retinal ontogenesis. Collagen IV and Fibronectin...
Motivation:
Formal verification is a computational approach that checks system correctness (in relation to a desired functionality). It has been widely used in engineering applications to verify that systems work correctly. Model checking, an algorithmic approach to verification, looks at whether a system model satisfies its requirements specifica...
The ability of microorganisms to regulate gene expression is thought to be critical for survival and growth during the development of polymicrobial biofilms such as dental plaque. The commensal dental plaque colonizer, Streptococcus gordonii, responds to cell-cell contact (coaggregation) with Actinomyces oris by regulating >20 genes, including thos...
uthors and contributions as published:
Jonathan Naylor, Harold Fellermann, Yuchun Ding,
Waleed K. Mohammed, Nicholas S. Jakubovics, Joy Mukherjee,
Catherine A. Biggs, Phillip C. Wright, and Natalio Krasnogor.
JN wrote the manuscript, developed the software and models
and performed data analysis. HF supervised the work, designed
the overall study, s...
An intriguing question in evolution is what would happen if one could “replay” life’s tape. Here, we explore the following hypothesis: when replaying the tape, the details (“decorations”) of the outcomes would vary but certain “invariants” might emerge across different life-tapes sharing similar initial conditions. We use large-scale simulations of...
Supplementary data and figures associated with this article.
(PDF)
Mutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To understand the molecular basis of this phenotype, we have generated RP type 11 (PRPF31-mutated) patient-specific retinal organoids and retinal pigment e...
We recently reported the design for a DNA nano-device that can record and store molecular signals. Here we present an evolutionary algorithm tailored to optimising nucleic acid sequences that predictively fold into our desired target structures. In our approach, a DNA device is first specified abstractly: the topology of the individual strands and...
Simbiotics is a spatially explicit multi-scale modeling platform for the design, simulation and analysis of bacterial populations. Systems ranging from planktonic cells and colonies, to biofilm formation and development may be modeled. Representation of biological systems in Simbiotics is flexible, user-defined processes may be in a variety of form...
Nanotechnology and synthetic biology are rapidly converging, with DNA origami being one of the leading bridging technologies. DNA origami was shown to work well in a wide array of biotic environments. However, the large majority of extant DNA origami scaffolds utilize bacteriophages or plasmid sequences thus severely limiting its future applicabili...
Recent advances Synthetic Biology are ushering a new practical computational substrate based on programmable information processing via biological cells. Due to the difficulties in orchestrating complex programmes using myriads of relatively simple, limited and highly stochastic processors such as living cells, robust computational technology to sp...
Background:
Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relation...
We present an implementation of an in vitro signal recorder based on DNA assembly and strand displacement. The signal recorder implements a stack data structure in which both data as well as operators are represented by single stranded DNA " bricks ". The stack grows by adding push and write bricks and shrinks in last-in-first-out manner by adding...
FuNeL is a protocol to infer functional networks from machine learning models. It is a general approach that uses BioHEL, a rule-based evolutionary classifier, to describe the expression samples as a set of rules and then infers interactions between genes that act together within rules to predict the samples class. FuNeL generates co-prediction net...
Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated
with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics.
Specifically, we...
Analysing genomic data and complex natural phenomena in computational terms enhances our comprehension of both nature and computation. Thus, a cross fertilization of algorithms and models for natural complex systems at molecular, cellular, or higher levels, became an active research area, and a more in depth investigation of mutual relationships, s...
In the past decades many definitions of complexity have been proposed. Most of these definitions are based either on Shannon's information theory or on Kolmogorov complexity; these two are often compared, but very few studies integrate the two ideas. In this article we introduce a new measure of complexity that builds on both of these theories. As...
The ultimate aim of Memetic Computing is the fully autonomous solution to complex optimisation problems. For a while now, the Memetic algorithms literature has been moving in the direction of ever increasing generalisation of optimisers initiated by seminal papers such as Krasnogor and Smith (IEEE Trans 9(5):474–488, 2005; Workshops Proceedings of...
Biological systems employ compartmentalization and other co-localization strategies in order to orchestrate a multitude of biochemical processes by simultaneously enabling “data hiding” and modularization. This article presents recent research that embraces compartmentalization and co-location as an organizational programmatic principle in syntheti...
This chapter gives an overview of an integrated software suite, the Infobiotics Workbench, which is based on a novel spatial discrete-stochastic P systems modelling framework. The Workbench incorporates three important features, simulation, model checking and optimisation. Its capability for building, analysing and optimising large spatially discre...
Unconventional computing is an area of research in which novel materials and paradigms are utilised to implement computation. Previously we have demonstrated how registers, logic gates and logic circuits can be implemented, unconventionally, with a biocompatible molecular switch, NitroBIPS, embedded in a polymer matrix. NitroBIPS and related molecu...
Data mining and knowledge discovery techniques have greatly progressed in the last decade. They are now able to handle larger and larger datasets, process heterogeneous information, integrate complex metadata, and extract and visualize new knowledge. Often these advances were driven by new challenges arising from real-world domains, with biology an...
Stochastic simulation algorithms (SSAs) are used to trace realistic trajectories of biochemical systems at low species concentrations. As the complexity of modelled bio-systems increases, it is important to select the best performing SSA. Numerous improvements to SSAs have been introduced but they each only tend to apply to a certain class of model...
Synthetic Biology aspires to design, compose and engineer biological systems that implement specified behaviour. When designing such systems, hypothesis testing via computational modelling and simulation is vital in order to reduce the need of costly wet lab experiments. As a case study, we discuss the use of computational modelling and stochastic...
Computational models are perceived as an attractive alternative to mathematical models, e.g. ordinary differential equations. These models incorporate a set of methods for specifying, modelling, testing and simulating biological systems. In addition, they can be analysed using algorithmic techniques, e.g. formal verification. This paper shows how f...
Biological systems employ compartmentalisation in order to orchestrate a multitude of biochemical processes by simultaneously enabling “data hiding” and modularisation. In this paper, we present recent research projects that embrace compartmentalisation as an organisational programmatic principle in synthetic biological and biomimetic systems. In t...