SJPedPanel: A Pan-Cancer Gene Panel for Childhood Malignancies to Enhance Cancer Monitoring and Early Detection.

Purpose: The purpose of the study was to design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples.

Experimental Design: In addition to 5,275 coding exons, SJPedPanel also covers 297 introns for fusions/structural variations and 7,590 polymorphic sites for copy-number alterations. Capture uniformity and limit of detection are determined by targeted sequencing of cell lines using dilution experiment.

SJPedPanel: A pan-cancer gene panel for childhood malignancies.

Background: Large scale genomics projects have identified driver alterations for most childhood cancers that provide reliable biomarkers for clinical diagnosis and disease monitoring using targeted sequencing. However, there is lack of a comprehensive panel that matches the list of known driver genes. Here we fill this gap by developing SJPedPanel for childhood cancers.

Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.

Oncogenic fusions formed through chromosomal rearrangements are hallmarks of childhood cancer that define cancer subtype, predict outcome, persist through treatment, and can be ideal therapeutic targets. However, mechanistic understanding of the etiology of oncogenic fusions remains elusive. Here we report a comprehensive detection of 272 oncogenic fusion gene pairs by using tumor transcriptome sequencing data from 5190 childhood cancer patients.

NSD2 E1099K drives relapse in pediatric acute lymphoblastic leukemia by disrupting 3D chromatin organization.

Background: The NSD2 p.E1099K (EK) mutation is shown to be enriched in patients with relapsed acute lymphoblastic leukemia (ALL), indicating a role in clonal evolution and drug resistance.

Results: To uncover 3D chromatin architecture-related mechanisms underlying drug resistance, we perform Hi-C on three B-ALL cell lines heterozygous for NSD2 EK.

Integrated Genomic Analysis Identifies UBTF Tandem Duplications as a Recurrent Lesion in Pediatric Acute Myeloid Leukemia.

Unlabelled: The genetics of relapsed pediatric acute myeloid leukemia (AML) has yet to be comprehensively defined. Here, we present the spectrum of genomic alterations in 136 relapsed pediatric AMLs. We identified recurrent exon 13 tandem duplications (TD) in upstream binding transcription factor (UBTF) in 9% of relapsed AML cases.

Chemotherapy and mismatch repair deficiency cooperate to fuel TP53 mutagenesis and ALL relapse.

Chemotherapy is a standard treatment for pediatric acute lymphoblastic leukemia (ALL), which sometimes relapses with chemoresistant features. However, whether acquired drug-resistance mutations in relapsed ALL pre-exist or are induced by treatment remains unknown. Here we provide direct evidence of a specific mechanism by which chemotherapy induces drug-resistance-associated mutations leading to relapse.

CBFB-MYH11 fusion transcripts distinguish acute myeloid leukemias with distinct molecular landscapes and outcomes.

transcripts and mutations predict relapse in AML. High-risk transcripts are associated with distinct transcriptional landscapes and upregulation of early hematopoiesis genes.

SequencErr: measuring and suppressing sequencer errors in next-generation sequencing data.

Background: There is currently no method to precisely measure the errors that occur in the sequencing instrument/sequencer, which is critical for next-generation sequencing applications aimed at discovering the genetic makeup of heterogeneous cellular populations.

Results: We propose a novel computational method, SequencErr, to address this challenge by measuring the base correspondence between overlapping regions in forward and reverse reads. An analysis of 3777 public datasets from 75 research institutions in 18 countries revealed the sequencer error rate to be ~ 10 per million (pm) and 1.

Analysis of solid tumor mutation profiles in liquid biopsy.

Liquid biopsy is increasingly gaining traction as an alternative to invasive solid tumor biopsies for prognosis, treatment decisions, and disease monitoring. Matched tumor-plasma samples were collected from 180 patients across different cancers with >90% of the samples below Stage IIIB. Tumors were profiled using next-generation sequencing (NGS) or quantitative PCR (qPCR), and the mutation status was queried in the matched plasma using digital platforms such as droplet digital PCR (ddCPR) or NGS for concordance.

The ISCB Student Council Internship Program: Expanding computational biology capacity worldwide.

Education and training are two essential ingredients for a successful career. On one hand, universities provide students a curriculum for specializing in one's field of study, and on the other, internships complement coursework and provide invaluable training experience for a fruitful career. Consequently, undergraduates and graduates are encouraged to undertake an internship during the course of their degree.

Characterization of bacterial community associated with phytoplankton bloom in a eutrophic lake in South Norway using 16S rRNA gene amplicon sequence analysis.

Interactions between different phytoplankton taxa and heterotrophic bacterial communities within aquatic environments can differentially support growth of various heterotrophic bacterial species. In this study, phytoplankton diversity was studied using traditional microscopic techniques and the bacterial communities associated with phytoplankton bloom were studied using High Throughput Sequencing (HTS) analysis of 16S rRNA gene amplicons from the V1-V3 and V3-V4 hypervariable regions. Samples were collected from Lake Akersvannet, a eutrophic lake in South Norway, during the growth season from June to August 2013.

Analysis of genotype diversity and evolution of Dengue virus serotype 2 using complete genomes.

Background: Dengue is one of the most common arboviral diseases prevalent worldwide and is caused by Dengue viruses (genus Flavivirus, family Flaviviridae). There are four serotypes of Dengue Virus (DENV-1 to DENV-4), each of which is further subdivided into distinct genotypes. DENV-2 is frequently associated with severe dengue infections and epidemics.

IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES).

Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5' untranslated regions (UTRs).

RV-Typer: A Web Server for Typing of Rhinoviruses Using Alignment-Free Approach.

Rhinoviruses (RV) are increasingly being reported to cause mild to severe infections of respiratory tract in humans. RV are antigenically the most diverse species of the genus Enterovirus and family Picornaviridae. There are three species of RV (RV-A, -B and -C), with 80, 32 and 55 serotypes/types, respectively.

Population structure and evolution of Rhinoviruses.

Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species.

WNV Typer: a server for genotyping of West Nile viruses using an alignment-free method based on a return time distribution.

West Nile virus (WNV), genus Flavivirus, family Flaviviridae, is a major cause of viral encephalitis with broad host range and global spread. The virus has undergone a series of evolutionary changes with emergence of various genotypic lineages that are known to differ in type and severity of the diseases caused. Currently, genotyping is carried out using molecular phylogeny of complete coding sequences and genotype is assigned based on proximity to reference genotypes in tree topology.

Alignment-free distance measure based on return time distribution for sequence analysis: applications to clustering, molecular phylogeny and subtyping.

The data deluge in post-genomic era demands development of novel data mining tools. Existing molecular phylogeny analyses (MPAs) developed for individual gene/protein sequences are alignment-based. However, the size of genomic data and uncertainties associated with alignments, necessitate development of alignment-free methods for MPA.