Article
Biodiversity Conservation
N. Pranzini, S. Bertolino, L. Santini
Summary: This study uses population density estimates to predict global population estimates for leopards and tigers. The results show that both species have higher densities in high productivity areas. The study also highlights the impact of environmental and anthropogenic factors on population density.
GLOBAL ECOLOGY AND CONSERVATION
(2023)
Article
Biochemical Research Methods
Rongtao Zheng, Zhijian Huang, Lei Deng
Summary: With the rapidly increasing volume of protein sequence and structure data, it is becoming increasingly important to automate the annotation of protein function at a large scale. This study proposes a large-scale approach called PredGO, which combines AlphaFold predicted three-dimensional structural information with other non-structural clues to accurately predict Gene Ontology (GO) functions for proteins. The computational results demonstrate that PredGO outperforms other existing methods in terms of both coverage and accuracy, making it a valuable tool in protein function prediction.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Changjun Peng, Dong-Dong Wu, Jin-Long Ren, Zhong-Liang Peng, Zhifei Ma, Wei Wu, Yunyun Lv, Zeng Wang, Cao Deng, Ke Jiang, Christopher L. Parkinson, Yin Qi, Zhi-Yi Zhang, Jia-Tang Li
Summary: By analyzing 14 newly assembled genomes, we investigated the genetic basis of snake phenotypes and conducted functional experiments to understand their morphological characteristics. We identified genes, regulatory elements, and structural variations that have potentially contributed to the evolution of snakes, such as limb loss, elongated body plan, asymmetrical lungs, sensory systems, and digestive adaptations. We also found genes and regulatory elements that might have shaped the evolution of vision, skeletal system and diet in blind snakes, and thermoreception in infrared-sensitive snakes. Our study provides new insights into the evolution and development of snakes and vertebrates.
Article
Water Resources
Pascal Castellazzi, Wolfgang Schmid
Summary: This study explores the value and challenges of using C-band InSAR ground deformation maps for large-scale aquifer depletion mapping in Australia. It reveals that factors such as high clay content, unfavorable land cover, and cropping activities can lead to non-attributable ground deformation signals in InSAR data.
JOURNAL OF HYDROLOGY-REGIONAL STUDIES
(2021)
Article
Oncology
Feicheng Wang, Nathan Palmer, Kathe Fox, Katherine P. P. Liao, Kun-Hsing Yu, Samuel C. C. Kou
Summary: Rheumatoid arthritis is associated with increased risks of developing various types of cancer, including lymphoma and lung cancer. However, the study found that the treatments commonly used for rheumatoid arthritis are not significantly linked to an increased cancer risk. This suggests that the pathophysiology of rheumatoid arthritis itself, rather than its treatments, plays a key role in the development of subsequent cancers.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Biochemical Research Methods
Kobe Janssen, Ramon Duran-Romana, Guy Bottu, Mainak Guharoy, Alexander Botzki, Frederic Rousseau, Joost Schymkowitz
Summary: This study presents a bioinformatics pipeline that allows for structural characterization from sequencing data using established stability and aggregation predictors such as FoldX, TANGO, and WALTZ, as well as the AlphaFold protein structure database. The pipeline provides high coverage for structural stability analysis and can be used to analyze proteome stability/damage in a given sample based on sequencing results.
BMC BIOINFORMATICS
(2023)
Article
Materials Science, Ceramics
R. Daniel Cassar, Saulo Martiello Mastelini, Tiago Botari, Edesio Alcobaca, C. P. L. F. Andre de Carvalho, D. Edgar Zanotto
Summary: The study investigated the predictive performance of three machine learning algorithms for six different glass properties, showing that for five properties, the induced predictive models had a comparable uncertainty to the usual data spread, while glasses with extremely low or high values of these properties had significantly higher prediction uncertainty. Furthermore, glasses containing chemical elements poorly represented in the training set yielded higher prediction errors. The analysis of SHAP values indicated key elements affecting the modeled properties, which can help with empirical compositional tuning and computer-aided inverse design of glass formulations.
CERAMICS INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Eloi Parlade, Eric Volta-Duran, Olivia Cano-Garrido, Julieta M. Sanchez, Ugutz Unzueta, Hector Lopez-Laguna, Naroa Serna, Montserrat Cano, Manuel Rodriguez-Mariscal, Esther Vazquez, Antonio Villaverde
Summary: Protein engineering using computational tools can be used to design stable protein materials for biomedical applications, increasing their viability. This method can be used as a routine tool in the design and optimization of protein materials prior to experimental testing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Psychology, Applied
Sudeep Bhatia, Christopher Y. Olivola, Nazli Bhatia, Amnah Ameen
Summary: This computational method utilizes high-dimensional semantic vectors derived from large-scale news media datasets to predict and identify leadership perceptions for prominent individuals. It outperforms other approaches and achieves accuracy rates comparable to human participants. The method also identifies dimensions associated with effective leadership and quantifies the extent of this association.
LEADERSHIP QUARTERLY
(2022)
Article
Biochemical Research Methods
Alexander W. Golinski, Zachary D. Schmitz, Gregory H. Nielsen, Bryce Johnson, Diya Saha, Sandhya Appiah, Benjamin J. Hackel, Stefano Martiniani
Summary: Engineered proteins are novel diagnostics, therapeutics, and catalysts. This study demonstrates the use of neural networks to predict protein developability from a high-throughput dataset and transfer this knowledge to predict recombinant expression beyond observed sequences. The analysis of learned amino acid embeddings highlights the importance of certain properties, such as cysteine, hydrophobicity, and charge, in improving protein developability. The study also identifies clusters of similar sequences with increased recombinant expression and explores the inferred expression landscape.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biochemical Research Methods
Zhaonan Zou, Michio Iwata, Yoshihiro Yamanishi, Shinya Oki
Summary: This study presents a computational method to elucidate the epigenetic landscape of drug responses by analyzing transcription factors. By predicting chemical-transcription factor-disease associations, this method can provide insights into new therapeutic targets and effects, guiding drug discovery and application.
BMC BIOINFORMATICS
(2022)
Review
Biochemistry & Molecular Biology
Benjamin B. V. Louis, Luciano A. Abriata
Summary: The prediction of protein stability upon mutations remains a challenging problem, with limitations in current methods and datasets. By analyzing a curated dataset and using a neural network, baseline predictions can be made accurately but require substantial corrections for actual stability changes. Recommendations for developers and dataset improvements are proposed based on these observations.
MOLECULAR BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael Gordon, Domenico Viganola, Anna Dreber, Magnus Johannesson, Thomas Pfeiffer
Summary: The study analyzed data from four research projects that predicted the outcomes of replication projects in social and behavioral sciences using human experts in prediction markets and surveys. The results show that there is information within the scientific community regarding the replicability of scientific findings, and that both surveys and prediction markets can be utilized to extract and aggregate this information. Prediction markets were able to determine replication outcomes with 73% accuracy, and both prediction market prices and average survey responses were correlated with outcomes.
Article
Computer Science, Software Engineering
Karsten Schatz, Juan Jose Franco-Moreno, Marco Schafer, Alexander S. Rose, Valerio Ferrario, Jurgen Pleiss, Pere-Pau Vazquez, Thomas Ertl, Michael Krone
Summary: When studying protein-ligand interactions, it is important to consider the overall behavior of the system rather than focusing solely on individual ligand molecules. To address visualization challenges, a preprocessing pipeline is used to aggregate movement data relative to a receptor protein, and a web-based visualization application combines multiple linked 2D and 3D views. This approach results in an interactive visualization system that is independent of underlying data size.
COMPUTER GRAPHICS FORUM
(2021)
Article
Biochemistry & Molecular Biology
Carter J. Wilson, Megan Chang, Mikko Karttunen, Wing-Yiu Choy
Summary: The study investigated the effects of 12 different cancer mutations on the protein KEAP1, providing structural insights into the mutants and suggesting stability as a possible target of cancer in KEAP1. The most prevalent mutation, R470C, showed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating a covalent modification as its mode of action.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biophysics
Francesco Pesce, Estella A. Newcombe, Pernille Seiffert, Emil E. Tranchant, Johan G. Olsen, Christy R. Grace, Birthe B. Kragelund, Kresten Lindorff-Larsen
Summary: Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins. To tackle the accuracy uncertainty issue in computing the hydrodynamic radius from atomic coordinates, conformational ensembles of intrinsically disordered proteins were built and compared with measurements of compaction. The Kirkwood-Riseman equation was found to provide the best description of the hydrodynamic radius probed by pulsed-field gradient NMR ex-periments.
BIOPHYSICAL JOURNAL
(2023)
Article
Biophysics
Johanna Katarina Sofie Tiemann, Henrike Zschach, Kresten Lindorff-Larsen, Amelie Stein
Summary: Next-generation sequencing of human genomes has identified millions of missense variants, some of which may contribute to the development of diseases by causing loss of protein function. In this study, we focused on missense variants in membrane proteins, which play crucial roles in cell signaling and recognition. Our findings suggest that loss of stability is a driving factor in the pathogenicity of membrane protein variants, highlighting the importance of understanding the underlying molecular processes.
BIOPHYSICAL JOURNAL
(2023)
Review
Oncology
Amanda B. Abildgaard, Sofie Nielsen, Inge Bernstein, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Accurate diagnosis and clinical interpretation of individual variants are crucial for the treatment of Lynch syndrome, a heritable cancer disease. Traditional protein variant classification methods are complex, but recent developments in high-throughput technologies and computational prediction tools offer new possibilities for assessing variants of unknown significance and gaining mechanistic insights into the disease.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Amanda B. Abildgaard, Vasileios Voutsinos, Soren D. Petersen, Fia B. Larsen, Caroline Kampmeyer, Kristoffer E. Johansson, Amelie Stein, Tommer Ravid, Claes Andreasson, Michael K. Jensen, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and chaperone-binding regions may function as PQC degrons. A canonical Hsp70-binding motif, the APPY peptide, functions as a dose-dependent PQC degron in yeast and human cells. The number of exposed Hsp70-binding sites in the yeast proteome correlates with reduced protein abundance and half-life.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kristoffer E. Johansson, Bayan Mashahreh, Rasmus Hartmann-Petersen, Tommer Ravid, Kresten Lindorff-Larsen
Summary: Effective proteome homeostasis is crucial for cell and organism survival. Cells have efficient quality control systems to monitor and remove misfolded proteins. The nature and sequence properties of quality-control degrons are still unknown.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fia B. Larsen, Matteo Cagiada, Jonas Dideriksen, Amelie Stein, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: Catechol-O-methyltransferase (COMT) is an important enzyme involved in the metabolism of neurotransmitters and catecholamine drugs, and its variation can affect pharmacokinetics and drug availability.
Review
Biotechnology & Applied Microbiology
Yixin Rong, Sheila Ingemann Jensen, Kresten Lindorff-Larsen, Alex Toftgaard Nielsen
Summary: The expression of correctly folded and functional heterologous proteins is crucial in biotechnological production processes. Bacterial platform organisms like E. coli are commonly used due to their proven suitability at an industrial scale, but can suffer from protein aggregation and low functional protein levels. This review explores cellular mechanisms influencing protein folding and expression across different organisms, and discusses experimental methods to improve protein folding, such as codon optimization and chaperone co-production.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Caroline Kampmeyer, Martin Gronbaek-Thygesen, Nicole Oelerich, Michael H. Tatham, Matteo Cagiada, Kresten Lindorff-Larsen, Wouter Boomsma, Kay Hofmann, Rasmus Hartmann-Petersen
Summary: Lysine is a common amino acid in the human proteome, but there are proteins that lack lysine residues. These lysine deserts are common in intrinsically disordered proteins involved in the ubiquitin-proteasome system. Introducing lysine residues can increase ubiquitylation of these proteins, and their stability and function may be affected. This avoidance of lysine residues may be an evolutionary mechanism to prevent unnecessary ubiquitylation in proteins closely involved with the ubiquitylation machinery.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kristoffer E. Johansson, Kresten Lindorff-Larsen, Jakob R. Winther
Summary: Identifying amino acid substitutions that improve both stability and function of a protein is a challenge in protein engineering. The Global Multi-Mutant Analysis (GMMA) method is used to identify beneficial substitutions across a large library of protein variants by analyzing multiply-substituted variants. Experimental results showed that the top-ranking substitutions progressively enhanced the function of GFP. Large libraries of multiply-substituted variants could provide valuable information for protein engineering.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yulian Gavrilov, Andreas Prestel, Kresten Lindorff-Larsen, Kaare Teilum
Summary: Slow conformational changes are important for protein function, but their impact on the overall folding stability is not well understood. This study investigates the effects of L49I and I57V substitutions on the slow conformational dynamics of CI2. The results show that these substitutions have minimal impact on the structure of the excited state, but the stability of the excited state is influenced by the stability of the main state. The interactions between substituted residues and water molecules play a role in linking subtle structural changes to slow conformational changes in the protein.
Editorial Material
Biochemistry & Molecular Biology
Sven Larsen-Ledet, Amelie Stein
Article
Multidisciplinary Sciences
Matteo Cagiada, Sandro Bottaro, Soren Lindemose, Signe M. Schenstrom, Amelie Stein, Rasmus Hartmann-Petersen, Kresten Lindorff-Larsen
Summary: The authors propose a machine-learning based method to predict functional sites in proteins by combining sequence and structural information. Proteins play important roles in biology, biotechnology, and pharmacology, and missense variants can cause disease. Discovering functional sites in proteins is challenging due to the lack of comprehensive data sets.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Sarah Gersing, Matteo Cagiada, Marinella Gebbia, Anette P. Gjesing, Atina G. Cote, Gireesh Seesankar, Roujia Li, Daniel Tabet, Jochen Weile, Amelie Stein, Anna L. Gloyn, Torben Hansen, Frederick P. Roth, Kresten Lindorff-Larsen, Rasmus Hartmann-Petersen
Summary: This study developed a multiplexed yeast complementation assay to measure the activity of GCK variants, capturing 97% of all possible missense and nonsense variants. The results showed that the activity scores correlated with in vitro catalytic efficiency, fasting glucose levels in carriers of GCK variants, and evolutionary conservation. This comprehensive assessment of GCK variant activity is important for variant interpretation and diagnosis, as well as for developing therapeutics targeting GCK.