scholarly journals Identifying Molecules as Biosignatures with Assembly Theory and Mass Spectrometry

2020 ◽  
Author(s):  
stuart Marshall ◽  
Cole Mathis ◽  
Emma Carrick ◽  
Graham Keenan ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
De Novo ◽  
Chemical Space ◽  
Outer Space ◽  
Molecular Graph ◽  
Molecular Assembly ◽  
Minimum Number ◽  
Intrinsic Complexity ◽  
Molecular Complexity ◽  
Detection Instrument ◽  
The Universe

<p><b>The search for evidence of life elsewhere in the universe is hard because it is not obvious what signatures are unique to life. Here we postulate that complex molecules found in high abundance are universal biosignatures as they cannot form by chance. To explore this, we developed the first intrinsic measure of molecular complexity that can be experimentally determined, and this is based upon a new approach called assembly theory which gives the molecular assembly number (MA) of a given molecule. MA allows us to compare the intrinsic complexity of molecules using the minimum number of steps required to construct the molecular graph starting from basic objects, and a probabilistic model shows how the probability of any given molecule forming randomly drops dramatically as its MA increases. To map chemical space, we calculated the MA of <i>ca.</i> 2.5 million compounds, and collected data which showed the complexity of a molecule can be experimentally determined by using three independent techniques including infra-red spectroscopy, nuclear magnetic resonance, and by fragmentation in a mass spectrometer, and this data has an excellent corelation with the values predicted from our assembly theory. We then set out to see if this approach could allow us to identify molecular biosignatures with a set of diverse samples from around the world, outer space, and the laboratory including prebiotic soups. <a>The results show that </a><a>there is a non-living to living threshold in MA complexity and the higher the MA for a given molecule, the more likely that it had to be produced by a biological process</a>. This work demonstrates it is possible to use this approach to build a life detection instrument that could be deployed on missions to extra-terrestrial locations to detect biosignatures, map the extent of life on Earth, and be used as a molecular complexity scale to quantify the constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital if we are going to find new life elsewhere in the universe or create <i>de-novo</i> life in the lab. </b></p>

scholarly journals Identifying Molecules as Biosignatures with Assembly Theory and Mass Spectrometry

2020 ◽  
Author(s):  
stuart Marshall ◽  
Cole Mathis ◽  
Emma Carrick ◽  
Graham Keenan ◽  
Geoffrey Cooper ◽  
...  
Keyword(s):  
De Novo ◽  
Chemical Space ◽  
Outer Space ◽  
Molecular Graph ◽  
Molecular Assembly ◽  
Minimum Number ◽  
Intrinsic Complexity ◽  
Molecular Complexity ◽  
Detection Instrument ◽  
The Universe

<p><b>The search for evidence of life elsewhere in the universe is hard because it is not obvious what signatures are unique to life. Here we postulate that complex molecules found in high abundance are universal biosignatures as they cannot form by chance. To explore this, we developed the first intrinsic measure of molecular complexity that can be experimentally determined, and this is based upon a new approach called assembly theory which gives the molecular assembly number (MA) of a given molecule. MA allows us to compare the intrinsic complexity of molecules using the minimum number of steps required to construct the molecular graph starting from basic objects, and a probabilistic model shows how the probability of any given molecule forming randomly drops dramatically as its MA increases. To map chemical space, we calculated the MA of <i>ca.</i> 2.5 million compounds, and collected data which showed the complexity of a molecule can be experimentally determined by using three independent techniques including infra-red spectroscopy, nuclear magnetic resonance, and by fragmentation in a mass spectrometer, and this data has an excellent corelation with the values predicted from our assembly theory. We then set out to see if this approach could allow us to identify molecular biosignatures with a set of diverse samples from around the world, outer space, and the laboratory including prebiotic soups. <a>The results show that </a><a>there is a non-living to living threshold in MA complexity and the higher the MA for a given molecule, the more likely that it had to be produced by a biological process</a>. This work demonstrates it is possible to use this approach to build a life detection instrument that could be deployed on missions to extra-terrestrial locations to detect biosignatures, map the extent of life on Earth, and be used as a molecular complexity scale to quantify the constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital if we are going to find new life elsewhere in the universe or create <i>de-novo</i> life in the lab. </b></p>

scholarly journals Identifying molecules as biosignatures with assembly theory and mass spectrometry

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stuart M. Marshall ◽  
Cole Mathis ◽  
Emma Carrick ◽  
Graham Keenan ◽  
Geoffrey J. T. Cooper ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
De Novo ◽  
Outer Space ◽  
Molecular Assembly ◽  
Detection Experiment ◽  
Complex Molecules ◽  
The World ◽  
Life Detection ◽  
Molecular Complexity ◽  
The Universe

AbstractThe search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry. This approach allows us to identify molecular biosignatures from a set of diverse samples from around the world, outer space, and the laboratory, demonstrating it is possible to build a life detection experiment based on MA that could be deployed to extraterrestrial locations, and used as a complexity scale to quantify constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital for finding life elsewhere in the universe or creating de-novo life in the lab.

scholarly journals Mapping the Molecular Tree of Life using Assembly Spaces

2020 ◽  
Author(s):  
Yu Liu ◽  
Cole Mathis ◽  
stuart Marshall ◽  
Leroy Cronin
Keyword(s):  
Prebiotic Chemistry ◽  
Structural Information ◽  
Chemical Space ◽  
Molecular Assembly ◽  
External Information ◽  
Molecular Tree ◽  
Minimum Number ◽  
Intrinsic Complexity ◽  
The Common ◽  
The Relationship

<p><b>The mapping of chemical space by the enumeration of graphs generates an infinite number of molecules, yet the experimental exploration of known chemical space shows that it appears to become sparser as the molecular weight of the compounds increases. What is needed is a way to explore chemical space that exploits the information encoded in known molecules to give access to unknown chemical space by building on the common conserved structures found in related families of molecules. Molecular assembly theory provides an approach to explore and compare the intrinsic complexity of molecules by the minimum number of steps needed to build up the target graphs, and here we show this can be applied to networks of molecules to explore the assembly properties of common motifs, rather than just focusing on molecules in isolation. This means molecular assembly theory can be used to define a tree of assembly spaces, allowing us to explore the accessible molecules connected to the tree, rather than the entire space of possible molecules. This approach provides a way to map the relationship between the molecules and their common fragments and thus measures the distribution of structural information collectively embedded in the molecules. We apply this approach to prebiotic chemistry, specifically the construction of RNA, and a family of opiates and plasticizers, as well as to gene sequences. This analysis allows us to quantify the amount of external information needed to assemble the tree and identify and predict new components in this family of molecules, based on the contingent information in the assembly spaces.</b></p>

scholarly journals Mapping the Molecular Tree of Life using Assembly Spaces

2020 ◽  
Author(s):  
Yu Liu ◽  
Cole Mathis ◽  
stuart Marshall ◽  
Leroy Cronin
Keyword(s):  
Prebiotic Chemistry ◽  
Structural Information ◽  
Chemical Space ◽  
Molecular Assembly ◽  
External Information ◽  
Molecular Tree ◽  
Minimum Number ◽  
Intrinsic Complexity ◽  
The Common ◽  
The Relationship

<p><b>The mapping of chemical space by the enumeration of graphs generates an infinite number of molecules, yet the experimental exploration of known chemical space shows that it appears to become sparser as the molecular weight of the compounds increases. What is needed is a way to explore chemical space that exploits the information encoded in known molecules to give access to unknown chemical space by building on the common conserved structures found in related families of molecules. Molecular assembly theory provides an approach to explore and compare the intrinsic complexity of molecules by the minimum number of steps needed to build up the target graphs, and here we show this can be applied to networks of molecules to explore the assembly properties of common motifs, rather than just focusing on molecules in isolation. This means molecular assembly theory can be used to define a tree of assembly spaces, allowing us to explore the accessible molecules connected to the tree, rather than the entire space of possible molecules. This approach provides a way to map the relationship between the molecules and their common fragments and thus measures the distribution of structural information collectively embedded in the molecules. We apply this approach to prebiotic chemistry, specifically the construction of RNA, and a family of opiates and plasticizers, as well as to gene sequences. This analysis allows us to quantify the amount of external information needed to assemble the tree and identify and predict new components in this family of molecules, based on the contingent information in the assembly spaces.</b></p>

Turning Aliens into Socialists

2010 ◽  
Vol 1 (1) ◽  
pp. 75-93
Author(s):  
Jessica Moberg
Keyword(s):  
Outer Space ◽  
The United States ◽  
Second World War ◽  
World War ◽  
History Of ◽  
Swedish History ◽  
Second World ◽  
The Universe ◽  
Highly Evolved

Immediately after the Second World War Sweden was struck by a wave of sightings of strange flying objects. In some cases these mass sightings resulted in panic, particularly after authorities failed to identify them. Decades later, these phenomena were interpreted by two members of the Swedish UFO movement, Erland Sandqvist and Gösta Rehn, as alien spaceships, or UFOs. Rehn argued that ‘[t]here is nothing so dramatic in the Swedish history of UFOs as this invasion of alien fly-things’ (Rehn 1969: 50). In this article the interpretation of such sightings proposed by these authors, namely that we are visited by extraterrestrials from outer space, is approached from the perspective of myth theory. According to this mythical theme, not only are we are not alone in the universe, but also the history of humankind has been shaped by encounters with more highly-evolved alien beings. In their modern day form, these kinds of ideas about aliens and UFOs originated in the United States. The reasoning of Sandqvist and Rehn exemplifies the localization process that took place as members of the Swedish UFO movement began to produce their own narratives about aliens and UFOs. The question I will address is: in what ways do these stories change in new contexts? Texts produced by the Swedish UFO movement are analyzed as a case study of this process.

On the parallels between cosmology and astrobiology: a transdisciplinary approach to the search for extraterrestrial life

2016 ◽  
Vol 15 (4) ◽  
pp. 251-260 ◽  
Author(s):  
Charles Morphy D. Santos ◽  
Leticia P. Alabi ◽  
Amâncio C. S. Friaça ◽  
Douglas Galante
Keyword(s):  
Extraterrestrial Life ◽  
Transdisciplinary Approach ◽  
Research Areas ◽  
Copernican Revolution ◽  
Scientific Status ◽  
Intrinsic Complexity ◽  
Experimental Approaches ◽  
The Universe

AbstractThe establishment of cosmology as a science provides a parallel to the building-up of the scientific status of astrobiology. The rise of astrobiological studies is explicitly based on a transdisciplinary approach that reminds of the Copernican Revolution, which eroded the basis of a closed Aristotelian worldview and reinforced the notion that the frontiers between disciplines are artificial. Given the intrinsic complexity of the astrobiological studies, with its multifactorial evidences and theoretical/experimental approaches, multi- and interdisciplinary perspectives are mandatory. Insulated expertise cannot grasp the vastness of the astrobiological issues. This need for integration among disciplines and research areas is antagonistic to excessive specialization and compartmentalization, allowing astrobiology to be qualified as a truly transdisciplinary enterprise. The present paper discusses the scientific status of astrobiological studies, based on the view that every kind of life, Earth-based or not, should be considered in a cosmic context. A confluence between ‘astro’ and ‘bio’ seeks the understanding of life as an emerging phenomenon in the universe. Thus, a new epistemological niche is opened, pointing to the development of a pluralistic vision for the philosophy of astrobiology.

scholarly journals SMILES-Based Deep Generative Scaffold Decorator for De-Novo Drug Design

2020 ◽  
Author(s):  
Josep Arús-Pous ◽  
Atanas Patronov ◽  
Esben Jannik Bjerrum ◽  
Christian Tyrchan ◽  
Jean-Louis Reymond ◽  
...  
Keyword(s):  
Data Augmentation ◽  
De Novo ◽  
Chemical Space ◽  
Generative Models ◽  
Synthetic Chemistry ◽  
Specific Knowledge ◽  
De Novo Drug Design ◽  
Wide Range ◽  
Small Set ◽  
Synthetic Approaches

Molecular generative models trained with small sets of molecules represented as SMILES strings are able to generate large regions of the chemical space. Unfortunately, due to the sequential nature of SMILES strings, these models are not able to generate molecules given a scaffold (i.e. partially-built molecules with explicit attachment points). Herein we report a new SMILES-based molecular generative architecture that generates molecules from scaffolds and can be trained from any arbitrary molecular set. This is possible thanks to a new molecular set pre-processing algorithm that exhaustively cuts all combinations of acyclic bonds of every molecule, obtaining a large number of scaffold-decorations combinations. Moreover, it serves as a data augmentation technique and can be readily coupled with randomized SMILES to obtain even better results with small sets. Two examples showcasing the potential of the architecture in medicinal and synthetic chemistry are described: First, models were trained with a training set obtained from a small set of Dopamine Receptor D2 (DRD2) active modulators and were able to meaningfully decorate a wide range of scaffolds and obtain molecular series predicted active on DRD2. Second, a larger set of drug-like molecules from ChEMBL was selectively sliced using synthetic chemistry constraints (RECAP rules). Moreover, the resulting scaffold-decorations were filtered to only allow decorations that were fragment-like. This allowed models trained with this dataset to selectively decorate diverse scaffolds with fragments that were generally predicted to be synthesizable and attachable to the scaffold using known synthetic approaches. In both cases, the models were already able to decorate molecules using specific knowledge without the need to add it with other techniques, such as reinforcement learning. We envision that this architecture will become a useful addition to the already existent architectures for de-novo molecular generation.

scholarly journals De Novo Molecule Design Through Molecular Generative Model Conditioned by 3D Information of Protein Binding Sites

2020 ◽  
Author(s):  
Mingyuan Xu ◽  
Ting Ran ◽  
Hongming Chen
Keyword(s):  
Protein Binding ◽  
De Novo ◽  
Structural Information ◽  
Chemical Space ◽  
Three Dimensional ◽  
Binding Pocket ◽  
Generative Model ◽  
Coarse Grained ◽  
Molecule Design ◽  
3D Information

<p><i>De novo</i> molecule design through molecular generative model is gaining increasing attention in recent years. Here a novel generative model was proposed by integrating the 3D structural information of the protein binding pocket into the conditional RNN (cRNN) model to control the generation of drug-like molecules. In this model, the composition of protein binding pocket is effectively characterized through a coarse-grain strategy and the three-dimensional information of the pocket can be represented by the sorted eigenvalues of the coulomb matrix (EGCM) of the coarse-grained atoms composing the binding pocket. In current work, we used our EGCM method and a previously reported binding pocket descriptor DeeplyTough to train cRNN models and compared their performance. It has been shown that the molecules generated with the control of protein environment information have a clear tendency on generating compounds with higher similarity to the original X-ray bound ligand than normal RNN model and also achieving better performance in terms of docking scores. Our results demonstrate the potential application of EGCM controlled generative model for the targeted molecule generation and guided exploration on the drug-like chemical space. </p><p> </p>

Exploring the combinatorial space of complete pathways to chemicals

2018 ◽  
Vol 46 (3) ◽  
pp. 513-522 ◽  
Author(s):  
Lin Wang ◽  
Chiam Yu Ng ◽  
Satyakam Dash ◽  
Costas D. Maranas
Keyword(s):  
De Novo ◽  
Design Procedure ◽  
Search Space ◽  
Performance Criterion ◽  
Mixed Integer ◽  
Design Tools ◽  
Minimum Number ◽  
Comprehensive Search ◽  
Synthetic Routes ◽  
Combinatorial Space

Computational pathway design tools often face the challenges of balancing the stoichiometry of co-metabolites and cofactors, and dealing with reaction rule utilization in a single workflow. To this end, we provide an overview of two complementary stoichiometry-based pathway design tools optStoic and novoStoic developed in our group to tackle these challenges. optStoic is designed to determine the stoichiometry of overall conversion first which optimizes a performance criterion (e.g. high carbon/energy efficiency) and ensures a comprehensive search of co-metabolites and cofactors. The procedure then identifies the minimum number of intervening reactions to connect the source and sink metabolites. We also further the pathway design procedure by expanding the search space to include both known and hypothetical reactions, represented by reaction rules, in a new tool termed novoStoic. Reaction rules are derived based on a mixed-integer linear programming (MILP) compatible reaction operator, which allow us to explore natural promiscuous enzymes, engineer candidate enzymes that are not already promiscuous as well as design de novo enzymes. The identified biochemical reaction rules then guide novoStoic to design routes that expand the currently known biotransformation space using a single MILP modeling procedure. We demonstrate the use of the two computational tools in pathway elucidation by designing novel synthetic routes for isobutanol.

4. Windows in the sky

2016 ◽  
pp. 39-46
Author(s):  
Geoff Cottrell
Keyword(s):  
Solar Radiation ◽  
Electromagnetic Radiation ◽  
Electromagnetic Waves ◽  
Outer Space ◽  
Cosmic Ray ◽  
High Energy ◽  
Electromagnetic Spectrum ◽  
Radio Waves ◽  
Transverse Waves ◽  
The Universe

The atmosphere influences much of what can be seen through a telescope. Most of the atmosphere lies within 16 km from the Earth’s surface. Further out, the air becomes thinner until it merges with outer space. In the ionosphere—a layer 75–1000 km high—neutral atoms are ionized by solar radiation and high-energy cosmic ray particles arriving from distant parts of the Universe. ‘Windows in the sky’ explains electromagnetic radiation and the electromagnetic spectrum from gamma rays through to visible light and radio waves. Electromagnetic waves are transverse waves that can be polarized. The atmosphere acts as a filter and blocks cosmic electromagnetic radiation. Atmospheric turbulence distorts starlight resulting in ‘twinkling’ stars.

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