HUMAP: Hierarchical Uniform Manifold Approximation and Projection.

Dimensionality reduction (DR) techniques help analysts to understand patterns in high-dimensional spaces. These techniques, often represented by scatter plots, are employed in diverse science domains and facilitate similarity analysis among clusters and data samples. For datasets containing many granularities or when analysis follows the information visualization mantra, hierarchical DR techniques are the most suitable approach since they present major structures beforehand and details on demand.

A Grid-Based Method for Removing Overlaps of Dimensionality Reduction Scatterplot Layouts.

Dimensionality Reduction (DR) scatterplot layouts have become a ubiquitous visualization tool for analyzing multidimensional datasets. Despite their popularity, such scatterplots suffer from occlusion, especially when informative glyphs are used to represent data instances, potentially obfuscating critical information for the analysis under execution. Different strategies have been devised to address this issue, either producing overlap-free layouts that lack the powerful capabilities of contemporary DR techniques in uncovering interesting data patterns or eliminating overlaps as a post-processing strategy.

The Flow of Trust: A Visualization Framework to Externalize, Explore, and Explain Trust in ML Applications.

We present a conceptual framework for the development of visual interactive techniques to formalize and externalize trust in machine learning (ML) workflows. Currently, trust in ML applications is an implicit process that takes place in the user's mind. As such, there is no method of feedback or communication of trust that can be acted upon.

FeatureEnVi: Visual Analytics for Feature Engineering Using Stepwise Selection and Semi-Automatic Extraction Approaches.

The machine learning (ML) life cycle involves a series of iterative steps, from the effective gathering and preparation of the data-including complex feature engineering processes-to the presentation and improvement of results, with various algorithms to choose from in every step. Feature engineering in particular can be very beneficial for ML, leading to numerous improvements such as boosting the predictive results, decreasing computational times, reducing excessive noise, and increasing the transparency behind the decisions taken during the training. Despite that, while several visual analytics tools exist to monitor and control the different stages of the ML life cycle (especially those related to data and algorithms), feature engineering support remains inadequate.

Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.

Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes.

PfGBP2 is a novel G-quadruplex binding protein in Plasmodium falciparum.

Guanine-quadruplexes (G4s) are non-canonical DNA structures that can regulate key biological processes such as transcription, replication and telomere maintenance in several organisms including eukaryotes, prokaryotes and viruses. Recent reports have identified the presence of G4s within the AT-rich genome of Plasmodium falciparum, the protozoan parasite causing malaria. In Plasmodium, potential G4-forming sequences (G4FS) are enriched in the telomeric and sub-telomeric regions of the genome where they are associated with telomere maintenance and recombination events within virulence genes.

Plasmodium falciparum sexual parasites regulate infected erythrocyte permeability.

To ensure the transport of nutrients necessary for their survival, Plasmodium falciparum parasites increase erythrocyte permeability to diverse solutes. These new permeation pathways (NPPs) have been extensively characterized in the pathogenic asexual parasite stages, however the existence of NPPs has never been investigated in gametocytes, the sexual stages responsible for transmission to mosquitoes. Here, we show that NPPs are still active in erythrocytes infected with immature gametocytes and that this activity declines along gametocyte maturation.

StackGenVis: Alignment of Data, Algorithms, and Models for Stacking Ensemble Learning Using Performance Metrics.

In machine learning (ML), ensemble methods-such as bagging, boosting, and stacking-are widely-established approaches that regularly achieve top-notch predictive performance. Stacking (also called "stacked generalization") is an ensemble method that combines heterogeneous base models, arranged in at least one layer, and then employs another metamodel to summarize the predictions of those models. Although it may be a highly-effective approach for increasing the predictive performance of ML, generating a stack of models from scratch can be a cumbersome trial-and-error process.

Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis.

Plasmodium falciparum gametocytes, the sexual stage responsible for malaria parasite transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated.

Toward a Quantitative Survey of Dimension Reduction Techniques.

Dimensionality reduction methods, also known as projections, are frequently used in multidimensional data exploration in machine learning, data science, and information visualization. Tens of such techniques have been proposed, aiming to address a wide set of requirements, such as ability to show the high-dimensional data structure, distance or neighborhood preservation, computational scalability, stability to data noise and/or outliers, and practical ease of use. However, it is far from clear for practitioners how to choose the best technique for a given use context.

Clipped histone H3 is integrated into nucleosomes of DNA replication genes in the human malaria parasite .

Post-translational modifications of histone H3 N-terminal tails are key epigenetic regulators of virulence gene expression and sexual commitment in the human malaria parasite Here, we identify proteolytic clipping of the N-terminal tail of nucleosome-associated histone H3 at amino acid position 21 as a new chromatin modification. A cathepsin C-like proteolytic clipping activity is observed in nuclear parasite extracts. Notably, an ectopically expressed version of clipped histone H3, PfH3p-HA, is targeted to the nucleus and integrates into mononucleosomes.

Plasmodium falciparum gametocyte-infected erythrocytes do not adhere to human primary erythroblasts.

Plasmodium falciparum gametocytes, the sexual stages responsible for malaria parasite transmission, develop in the human bone marrow parenchyma in proximity to the erythroblastic islands. Yet, mechanisms underlying gametocytes interactions with these islands are unknown. Here, we have investigated whether gametocyte-infected erythrocytes (GIE) adhere to erythroid precursors, and whether a putative adhesion may be mediated by a mechanism similar to the adhesion of erythrocytes infected with P.

An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum.

Variegated surface antigen expression is key to chronic infection and pathogenesis of the human malaria parasite Plasmodium falciparum. This protozoan parasite expresses distinct surface molecules that are encoded by clonally variant gene families such as var, rif and stevor. The molecular mechanisms governing activation of individual members remain ill-defined.

First efficient CRISPR-Cas9-mediated genome editing in Leishmania parasites.

Protozoan pathogens that cause leishmaniasis in humans are relatively refractory to genetic manipulation. In this work, we implemented the CRISPR-Cas9 system in Leishmania parasites and demonstrated its efficient use for genome editing. The Cas9 endonuclease was expressed under the control of the Dihydrofolate Reductase-Thymidylate Synthase (DHFR-TS) promoter and the single guide RNA was produced under the control of the U6snRNA promoter and terminator.

Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria.

Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. Expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown.

Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system.

Genome manipulation in the malaria parasite Plasmodium falciparum remains largely intractable and improved genomic tools are needed to further understand pathogenesis and drug resistance. We demonstrated the CRISPR-Cas9 system for use in P. falciparum by disrupting chromosomal loci and generating marker-free, single-nucleotide substitutions with high efficiency.

Strand-specific RNA-Seq reveals widespread and developmentally regulated transcription of natural antisense transcripts in Plasmodium falciparum.

Background: Advances in high-throughput sequencing have led to the discovery of widespread transcription of natural antisense transcripts (NATs) in a large number of organisms, where these transcripts have been shown to play important roles in the regulation of gene expression. Likewise, the existence of NATs has been observed in Plasmodium but our understanding towards their genome-wide distribution remains incomplete due to the limited depth and uncertainties in the level of strand specificity of previous datasets.

Results: To gain insights into the genome-wide distribution of NATs in P.

Differential expression profiles in the midgut of Triatoma infestans infected with Trypanosoma cruzi.

Chagas disease, or American trypanosomiasis, is a parasitic disease caused by the protozoan Trypanosoma cruzi and is transmitted by insects from the Triatominae subfamily. To identify components involved in the protozoan-vector relationship, we constructed and analyzed cDNA libraries from RNA isolated from the midguts of uninfected and T. cruzi-infected Triatoma infestans, which are major vectors of Chagas disease.

Nuclear pores and perinuclear expression sites of var and ribosomal DNA genes correspond to physically distinct regions in Plasmodium falciparum.

The human malaria parasite Plasmodium falciparum modifies the erythrocyte it infects by exporting variant proteins to the host cell surface. The var gene family that codes for a large, variant adhesive surface protein called P. falciparum erythrocyte membrane protein 1 (PfEMP1) plays a particular role in this process, which is linked to pathogenesis and immune evasion.

Differential infectivity by the oral route of Trypanosoma cruzi lineages derived from Y strain.

Background: Diversity of T. cruzi strains is a central problem in Chagas disease research because of its correlation with the wide range of clinical manifestations and the biogeographical parasite distribution. The role played by parasite microdiversity in Chagas disease epidemiology is still debatable.

Tigutcystatin, a cysteine protease inhibitor from Triatoma infestans midgut expressed in response to Trypanosoma cruzi.

The insect Triatoma infestans is a vector of Trypanosoma cruzi, the etiological agent of Chagas disease. A cDNA library was constructed from T. infestans anterior midgut, and 244 clones were sequenced.

A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells.

Background: Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd(2) [S((-))C(2), N-dmpa](2) (μ-dppe)Cl(2)} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice.

Starvation and rapamycin differentially regulate host cell lysosome exocytosis and invasion by Trypanosoma cruzi metacyclic forms.

The molecular mechanisms of host cell invasion by T. cruzi metacyclic trypomastigotes (MT), the developmental forms that initiate infection in the mammalian host, are only partially understood. Here we aimed at further identifying the target cell components involved in signalling cascades leading to MT internalization, and demonstrate for the first time the participation of mammalian target of rapamycin (mTOR).