GIInger predicts homologous recombination deficiency and patient response to PARPi treatment from shallow genomic profiles.

Homologous recombination deficiency (HRD) is a predictive biomarker for poly(ADP-ribose) polymerase 1 inhibitor (PARPi) sensitivity. Routine HRD testing relies on identifying BRCA mutations, but additional HRD-positive patients can be identified by measuring genomic instability (GI), a consequence of HRD. However, the cost and complexity of available solutions hamper GI testing.

Developmental dynamics of lncRNAs across mammalian organs and species.

Although many long noncoding RNAs (lncRNAs) have been identified in human and other mammalian genomes, there has been limited systematic functional characterization of these elements. In particular, the contribution of lncRNAs to organ development remains largely unexplored. Here we analyse the expression patterns of lncRNAs across developmental time points in seven major organs, from early organogenesis to adulthood, in seven species (human, rhesus macaque, mouse, rat, rabbit, opossum and chicken).

Convergent origination of a -like dosage compensation mechanism in a reptile lineage.

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage.

PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3' UTRs and coding sequences.

The purpose of the proposed web server, publicly available at http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies primarily mRNA transcripts targeted in their 3' untranslated regions (3' UTRs), and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding sequences (CDSs).

Genome sequence of the Drosophila melanogaster male-killing Spiroplasma strain MSRO endosymbiont.

Unlabelled: Spiroplasmas are helical and motile members of a cell wall-less eubacterial group called Mollicutes. Although all spiroplasmas are associated with arthropods, they exhibit great diversity with respect to both their modes of transmission and their effects on their hosts; ranging from horizontally transmitted pathogens and commensals to endosymbionts that are transmitted transovarially (i.e.

Origins and functional evolution of Y chromosomes across mammals.

Y chromosomes underlie sex determination in mammals, but their repeat-rich nature has hampered sequencing and associated evolutionary studies. Here we trace Y evolution across 15 representative mammals on the basis of high-throughput genome and transcriptome sequencing. We uncover three independent sex chromosome originations in mammals and birds (the outgroup).

Searching the coding region for microRNA targets.

Finding microRNA targets in the coding region is difficult due to the overwhelming signal encoding the amino acid sequence. Here, we introduce an algorithm (called PACCMIT-CDS) that finds potential microRNA targets within coding sequences by searching for conserved motifs that are complementary to the microRNA seed region and also overrepresented in comparison with a background model preserving both codon usage and amino acid sequence. Precision and sensitivity of PACCMIT-CDS are evaluated using PAR-CLIP and proteomics data sets.

Analysis of the accessibility of CLIP bound sites reveals that nucleation of the miRNA:mRNA pairing occurs preferentially at the 3'-end of the seed match.

To find out whether the AGO-miRNA complex is more sensitive to the accessibility of a particular region inside the seed match, we analyze in detail the accessibility of a wide set of miRNA binding sites validated by PAR-CLIP and HITS-CLIP experiments. Our analysis reveals that nucleotides at the 3'-end of bound seed matches are significantly more accessible than nucleotides at the 5'-end as well as nucleotides at any positions in the unbound seed matches. We show that the accessibility of a single nucleotide at the 3'-end is more effective than the accessibility of several nucleotides at the 5'-end in discriminating between functional and nonfunctional binding sites.

Optimal use of conservation and accessibility filters in microRNA target prediction.

It is generally accepted that filtering microRNA (miRNA) target predictions by conservation or by accessibility can reduce the false discovery rate. However, these two strategies are usually not exploited in a combined and flexible manner. Here, we introduce PACCMIT, a flexible method that filters miRNA binding sites by their conservation, accessibility, or both.

Efficient use of accessibility in microRNA target prediction.

Considering accessibility of the 3'UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by the sum of the opening and hybridization energies, used in currently available algorithms, is not an efficient way to rank predictions. Instead, we describe an algorithm which also considers only the accessible binding sites but which ranks predictions according to over-representation.

Characterization of activity landscapes using 2D and 3D similarity methods: consensus activity cliffs.

Activity landscape characterization has been demonstrated to be a valuable tool in lead optimization, virtual screening, and computational modeling of active compounds. In this work, we present a general protocol to explore systematically the activity landscape of a lead series using 11 2D and 3D structural representations. As a test case we employed a set of 48 bicyclic guanidines (BCGs) with kappa-opioid receptor binding affinity, identified in our group.

Radial scan of the molecular electrostatic potential of RNA double helices: an application to the enzyme-tRNA recognition.

We introduced a method to characterize quantitatively the molecular electrostatic potential (MEP) of the minor and major grooves of base pairs located at nucleic acid double helices. By means of a radial MEP scan, we obtained a n-tuple of potential values corresponding to each groove, which can be analyzed by plotting the MEP values as a function of the angle in the radial scan. We studied base pairs of two different tRNAs, relevant in the recognition process with their cognate aminoacyl tRNA synthetases (aaRSs), in order to correlate their electrostatic behavior with the corresponding aminoacylation activity.

Graph theoretical similarity approach to compare molecular electrostatic potentials.

In this work we introduce a graph theoretical method to compare MEPs, which is independent of molecular alignment. It is based on the edit distance of weighted rooted trees, which encode the geometrical and topological information of Negative Molecular Isopotential Surfaces. A meaningful chemical classification of a set of 46 molecules with different functional groups was achieved.