Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform.

The majority of cancer deaths are caused by solid tumors, where the four most prevalent cancers (breast, lung, colorectal and prostate) account for more than 60% of all cases (1). Tumor cell heterogeneity driven by variable cancer microenvironments, such as hypoxia, is a key determinant of therapeutic outcome. We developed a novel culture protocol, termed the Long-Term Hypoxia (LTHY) time course, to recapitulate the gradual development of severe hypoxia seen in vivo to mimic conditions observed in primary tumors.

Automatic recognition of complementary strands: lessons regarding machine learning abilities in RNA folding.

Prediction of RNA secondary structure from single sequences still needs substantial improvements. The application of machine learning (ML) to this problem has become increasingly popular. However, ML algorithms are prone to overfitting, limiting the ability to learn more about the inherent mechanisms governing RNA folding.

D-ORB: A Web Server to Extract Structural Features of Related But Unaligned RNA Sequences.

Identifying the common structural elements of functionally related RNA sequences (family) is usually based on an alignment of the sequences, which is often subject to human bias and may not be accurate. The resulting covariance model (CM) provides probabilities for each base to covary with another, which allows to support evolutionarily the formation of double helical regions and possibly pseudoknots. The coexistence of alternative folds in RNA, resulting from its dynamic nature, may lead to the potential omission of motifs by CM.

The DynaSig-ML Python package: automated learning of biomolecular dynamics-function relationships.

Unlabelled: The DynaSig-ML ('Dynamical Signatures-Machine Learning') Python package allows the efficient, user-friendly exploration of 3D dynamics-function relationships in biomolecules, using datasets of experimental measures from large numbers of sequence variants. It does so by predicting 3D structural dynamics for every variant using the Elastic Network Contact Model (ENCoM), a sequence-sensitive coarse-grained normal mode analysis model. Dynamical Signatures represent the fluctuation at every position in the biomolecule and are used as features fed into machine learning models of the user's choice.

Sequence-sensitive elastic network captures dynamical features necessary for miR-125a maturation.

The Elastic Network Contact Model (ENCoM) is a coarse-grained normal mode analysis (NMA) model unique in its all-atom sensitivity to the sequence of the studied macromolecule and thus to the effect of mutations. We adapted ENCoM to simulate the dynamics of ribonucleic acid (RNA) molecules, benchmarked its performance against other popular NMA models and used it to study the 3D structural dynamics of human microRNA miR-125a, leveraging high-throughput experimental maturation efficiency data of over 26 000 sequence variants. We also introduce a novel way of using dynamical information from NMA to train multivariate linear regression models, with the purpose of highlighting the most salient contributions of dynamics to function.