Hyperdimensional computing: A fast, robust, and interpretable paradigm for biological data.

Advances in bioinformatics are primarily due to new algorithms for processing diverse biological data sources. While sophisticated alignment algorithms have been pivotal in analyzing biological sequences, deep learning has substantially transformed bioinformatics, addressing sequence, structure, and functional analyses. However, these methods are incredibly data-hungry, compute-intensive, and hard to interpret.

Loss-of-Imprinting of HM13 Leads to Poor Prognosis in Clear Cell Renal Cell Carcinoma.

Genomic imprinting refers to the epigenetic silencing of one of both alleles in a parent-of-origin-specific manner, particularly in genes regulating growth and development. Impaired genomic imprinting leading to the activation of the silenced allele, also called canonical loss-of-imprinting (LOI), is considered an early factor in oncogenesis. As LOI studies in clear cell renal cell carcinoma (ccRCC) are limited to , we performed a genome-wide analysis in 128 kidney normal solid tissue and 240 stage 1 ccRCC samples (TCGA RNA-seq data) to screen for canonical LOI in early oncogenesis.

Quantitative transcriptomic and epigenomic data analysis: a primer.

The advent of microarray and second generation sequencing technology has revolutionized the field of molecular biology, allowing researchers to quantitatively assess transcriptomic and epigenomic features in a comprehensive and cost-efficient manner. Moreover, technical advancements have pushed the resolution of these sequencing techniques to the single cell level. As a result, the bottleneck of molecular biology research has shifted from the bench to the subsequent omics data analysis.

A Genomic Urine Assay for Surveillance of Patients with Bladder Cancer Treated with Radiotherapy.

Background: Patients with muscle-invasive bladder cancer (MIBC) who receive radiotherapy with curative intent are followed by imaging, cystoscopy, and urine cytology. However, interpretation of cytology and cystoscopy is hampered by the impact of ionizing radiation on cells.

Objective: To assess the diagnostic performance of a genomic urine assay to detect urinary tract recurrences in patients with MIBC treated by (chemo)radiation.

The role of Helicobacter suis, Fusobacterium gastrosuis, and the pars oesophageal microbiota in gastric ulceration in slaughter pigs receiving meal or pelleted feed.

This study investigated the role of causative infectious agents in ulceration of the non-glandular part of the porcine stomach (pars oesophagea). In total, 150 stomachs from slaughter pigs were included, 75 from pigs that received a meal feed, 75 from pigs that received an equivalent pelleted feed with a smaller particle size. The pars oesophagea was macroscopically examined after slaughter.

HIV-PULSE: a long-read sequencing assay for high-throughput near full-length HIV-1 proviral genome characterization.

A deep understanding of the composition of the HIV-1 reservoir is necessary for the development of targeted therapies and the evaluation of curative efforts. However, current near full-length (NFL) HIV-1 proviral genome sequencing assays are based on labor-intensive and costly principles of repeated PCRs at limiting dilution, restricting their scalability. To address this, we developed a high-throughput, long-read sequencing assay called HIV-PULSE (HIV Proviral UMI-mediated Long-read Sequencing).

Cost-effectiveness of an urinary biomarker panel in combination with MRI for prostate cancer diagnosis.

Purpose: The health impact and cost-effectiveness of the biomarker test SelectMDx were evaluated when used in combination with MRI, in two US populations: biopsy naïve men and men with a previous negative biopsy.

Methods: Using a decision model, the current MRI strategy was compared with two SelectMDx strategies: SelectMDx used before MRI to select men for MRI and SelectMDx used after a negative MRI to select men for biopsy. Parameters were informed by the literature most relevant for both populations.

HIV-PULSE: A long-read sequencing assay for high-throughput near full-length HIV-1 proviral genome characterization.

A deep understanding of the composition of the HIV-1 reservoir is necessary for the development of targeted therapies and the evaluation of curative efforts. However, current near full-length (NFL) HIV-1 proviral genome sequencing assays are based on labor-intensive and costly principles of repeated PCRs at limiting dilution, restricting their scalability. To address this, we developed a high-throughput, long-read sequencing assay called HIV-PULSE (HIV P roviral U MI-mediated L ong-read Se quencing).

Challenges in neoantigen-directed therapeutics.

A fundamental prerequisite for the efficacy of cancer immunotherapy is the presence of functional, antigen-specific T cells within the tumor. Neoantigen-directed therapy is a promising strategy that aims at targeting the host's immune response against tumor-specific antigens, thereby eradicating cancer cells. Initial forays have been made in clinical environments utilizing vaccines and adoptive cell therapy; however, many challenges lie ahead.

Haplotyping pharmacogenes using TLA combined with Illumina or Nanopore sequencing.

The currently used pharmacogenetic genotyping assays offer limited haplotype information, which can potentially cause specific functional effects to be missed. This study tested if Targeted Locus Amplification (TLA), when using non-patient-specific primers combined with Illumina or Nanopore sequencing, can offer an advantage in terms of accurate phasing. The TLA method selectively amplifies and sequences entire genes based on crosslinking DNA in close physical proximity.

A Urine-based Genomic Assay Improves Risk Stratification for Patients with High-risk Hematuria Stratified According to the American Urological Association Guidelines.

Background: According to the recent American Urological Association (AUA) guideline on hematuria, patients are stratified into groups with low, intermediate, and high risk of urothelial carcinoma (UC). These risk groups are based on clinical factors and do not incorporate urine-based tumor markers.

Objective: To evaluate whether a urine-based genomic assay improves the redefined AUA risk stratification for hematuria.

Technical considerations in PCR-based assay design for diagnostic DNA methylation cancer biomarkers.

Background: DNA methylation biomarkers for early detection, risk stratification and treatment response in cancer have been of great interest over the past decades. Nevertheless, clinical implementation of these biomarkers is limited, as only < 1% of the identified biomarkers is translated into a clinical or commercial setting. Technical factors such as a suboptimal genomic location of the assay and inefficient primer or probe design have been emphasized as important pitfalls in biomarker research.

PhaLP: A Database for the Study of Phage Lytic Proteins and Their Evolution.

Phage lytic proteins are a clinically advanced class of novel enzyme-based antibiotics, so-called enzybiotics. A growing community of researchers develops phage lytic proteins with the perspective of their use as enzybiotics. A successful translation of enzybiotics to the market requires well-considered selections of phage lytic proteins in early research stages.

Spectral Prediction Features as a Solution for the Search Space Size Problem in Proteogenomics.

Proteogenomics approaches often struggle with the distinction between true and false peptide-to-spectrum matches as the database size enlarges. However, features extracted from tandem mass spectrometry intensity predictors can enhance the peptide identification rate and can provide extra confidence for peptide-to-spectrum matching in a proteogenomics context. To that end, features from the spectral intensity pattern predictors MSPIP and Prosit were combined with the canonical scores from MaxQuant in the Percolator postprocessing tool for protein sequence databases constructed out of ribosome profiling and nanopore RNA-Seq analyses.

DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon.

Song learning in zebra finches () is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development.

Single cell epigenetic visualization assay.

Characterization of the epigenetic status of individual cells remains a challenge. Current sequencing approaches have limited coverage, and it is difficult to assign an epigenetic status to the transcription state of individual gene alleles in the same cell. To address these limitations, a targeted microscopy-based epigenetic visualization assay (EVA) was developed for detection and quantification of epigenetic marks at genes of interest in single cells.

Evaluation of the New American Urological Association Guidelines Risk Classification for Hematuria.

Purpose: Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline.

Materials And Methods: This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria.

Underestimated effect of intragenic HIV-1 DNA methylation on viral transcription in infected individuals.

Background: The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly understood or characterized.

Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

Background: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario.

Methods: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI).

A Urine Based Genomic Assay to Triage Patients with Hematuria for Cystoscopy.

Purpose: Current clinical guidelines recommend cystoscopy in patients who present with hematuria to rule out a bladder tumor. We evaluated whether our previously developed urine assay was able to triage patients with hematuria for cystoscopy in a large prospective cohort.

Materials And Methods: A urine sample was collected before cystoscopy and mutation/methylation status of 6 genes was determined on cellular DNA.

Clinically significant Prostate Cancer diagnosed using a urinary molecular biomarker-based risk score: two case reports.

Background: Identifying men for a repeat prostate biopsy is a conundrum to urologists. Risk calculators (RCs) such as the European Randomized Study of Screening for Prostate Cancer (ERSPC) RCs have been developed to predict the outcome of prostate biopsies and have been shown to improve diagnostic accuracy compared to PSA alone. However, it was recently shown that the outcome for high-grade prostate cancer (PCa) upon biopsy tended to be underestimated in men with previous negative biopsies using ERSPC RC model 4.

Urinary Molecular Biomarker Test Impacts Prostate Biopsy Decision Making in Clinical Practice.

Introduction: There is an unmet need for noninvasive methods to better identify patients at increased risk for clinically significant prostate cancer. SelectMDx® is a molecular urine test validated for the detection of Gleason score 7 and higher cancers (ISUP [International Society of Urological Pathology] Grade Group 2-5). In this multicenter trial we evaluated the test's impact on prostate biopsy decision making in clinical practice.

MEXPRESS update 2019.

The recent growth in the number of publicly available cancer omics databases has been accompanied by the development of various tools that allow researchers to visually explore these data. In 2015, we built MEXPRESS, an online tool for the integration and visualization of gene expression, DNA methylation and clinical data from The Cancer Genome Atlas (TCGA), a large collection of publicly available multi-omics cancer data. MEXPRESS addresses the need for an easy-to-use, interactive application that allows researchers to identify dysregulated genes and their clinical relevance in cancer.