Machine learning methods for histopathological image analysis

Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions.Comment: 23 pages, 4 figure

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

A Critical Review on Project-Based Learning in Japanese Secondary Education

Project-based learning (PBL) implementation in Japanese secondary school education has more momentum than ever before. However, PBL implementation in high schools is very limited. The purpose of this paper is to critically review the early stages of PBL implementation in Japanese secondary school education, which is currently in the process of signifcant reform. Why is PBL receiving so much focus in the reforms being made in the Japanese secondary school education now? What kinds of practices are schools following that explain the challenges facing secondary schools in implementing PBL? PBL in Japan has been implemented in a move towards experiential education since the early 20th century in correlation with two compatible approaches; systematic education and experiential education. The current challenge of PBL in secondary schools is to actualize PBL practices in schools through innovating the mindset of schools and teachers to move from systematic education to experiential education under the pressure of primary and secondary school curriculum reform and high school and university articulation reform. To make the PBL approach more effective in schools, setting a driving question based in the real world is effective. In that sense, PBL based on community revitalization and sustainability are powerful. In order to examine the context and effect of PBL in detail, we refer to how PBL has been implemented in schools with the encouragement of the Japan Innovative Schools Network (ISN), supported by the OECD. Global collaboration has a powerful effect on Japanese secondary school students. This paper intends to contribute to global educational reform efforts, since education reform is a major concern for every country

Pathology Images of Scanners and Mobilephones (PLISM) - Original Whole Slide Images Dataset

The Pathology Images of Scanners and Mobilephones (PLISM) dataset was created for the evaluation of AI models’ robustness to domain shifts. PLISM is the first group-wised pathological image dataset that encompasses diverse tissue types stained under 13 H&E conditions, with multiple imaging media, including smartphones (7 scanners and 6 smartphones).The PLISM-orginal subset consists of 91 original WSIs before image registration. Color and texture in digital pathology images are affected by H&E stain conditions (e.g. Harris or Carrazi) and digitalization devices (e.g. slide scanners or smartphones), which cause inter-institutional domain shifts.The extension of each WSI file is .svs, .ndpi, or .tiff.See the other subsets of the PLISM dataset in the Collection at https://doi.org/10.25452/figshare.plus.c.6773925</p

HER2 Heterogeneity Is Associated with Poor Survival in HER2-Positive Breast Cancer

Intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity has been reported in 16&ndash;36% of HER2-positive breast cancer and its clinical impact is under discussion. We examined the biological effects of HER2-heterogeneity on mouse models and analyzed metastatic brains by RNA sequence analysis. A metastatic mouse model was developed using 231-Luc (triple negative cells) and 2 HER2-positive cell lines, namely, HER2-60 and HER2-90 which showed heterogeneous and monotonous HER2 expressions, respectively. Metastatic lesions developed in 3 weeks in all the mice injected with HER2-60 cells, and in 69% of the mice injected with HER2-90 and 87.5% of the mice injected with 231-Luc. The median survival days of mice injected with 231-Luc, HER2-60, and HER2-90 cells were 29 (n = 24), 24 (n = 22) and 30 (n = 13) days, respectively. RNA sequence analysis showed that CASP-1 and its related genes were significantly downregulated in metastatic brain tumors with HER2-60 cells. The low expression of caspase-1 could be a new prognostic biomarker for early relapse in HER2-positive breast cancer

Genome-wide detection of human copy number variations using high-density DNA oligonucleotide arrays

Recent reports indicate that copy number variations (CNVs) within the human genome contribute to nucleotide diversity to a larger extent than single nucleotide polymorphisms (SNPs). In addition, the contribution of CNVs to human disease susceptibility may be greater than previously expected, although a complete understanding of the phenotypic consequences of CNVs is incomplete. We have recently reported a comprehensive view of CNVs among 270 HapMap samples using high-density SNP genotyping arrays and BAC array CGH. In this report, we describe a novel algorithm using Affymetrix GeneChip Human Mapping 500K Early Access (500K EA) arrays that identified 1203 CNVs ranging in size from 960 bp to 3.4 Mb. The algorithm consists of three steps: (1) Intensity pre-processing to improve the resolution between pairwise comparisons by directly estimating the allele-specific affinity as well as to reduce signal noise by incorporating probe and target sequence characteristics via an improved version of the Genomic Imbalance Map (GIM) algorithm; (2) CNV extraction using an adapted SW-ARRAY procedure to automatically and robustly detect candidate CNV regions; and (3) copy number inference in which all pairwise comparisons are summarized to more precisely define CNV boundaries and accurately estimate CNV copy number. Independent testing of a subset of CNVs by quantitative PCR and mass spectrometry demonstrated a >90% verification rate. The use of high-resolution oligonucleotide arrays relative to other methods may allow more precise boundary information to be extracted, thereby enabling a more accurate analysis of the relationship between CNVs and other genomic features

Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration

Abstract Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages