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Artificial Intelligence analysis of the immune-checkpoint and immuno-oncology in B-cell non-Hodgkin lymphoma

Research Project

Project/Area Number 23K06454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionTokai University

Principal Investigator

カレーラス ジュアキム  東海大学, 医学部, 准教授 (90637191)

Project Period (FY) 2023-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2024: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsimmuno-oncology / non-Hodgkin lymphoma / artificial intelligence / deep learning / neural network / colitis / lymphoma / targeted sequencing / immune microenvironment / immune checkpoint / molecular pathology / hematological neoplasia / NGS / リンパ腫 / 免疫腫瘍学 / 人工知能 / 免疫チェックポイント / 次世代シーケンシング
Outline of Research at the Start

この研究では、集学的アプローチを使用してリンパ腫の免疫チェックポイントを分析しています。B細胞性リンパ腫の解析を行います。重要なマーカーは、PD-L1、CSF1R、IL-10 などです。免疫組織化学、遺伝子発現解析、コピー数・LOH解析、次世代標的変異解析などを実施します。解析には、従来のバイオインフォマティクスだけでなく、人工知能(機械学習、ニューラルネットワーク)なども含まれます。

Outline of Annual Research Achievements

We have optimized the immunohistochemistry of immuno-oncology markers. The markers have been tested in non-Hodgkin lymphoma and in B-cell lymphomas such as FL, DLBCL, MALT, etc. Additionally, analysis have been performed in inflammatory bowel conditions such as ulcerative colitis, Chron's disease, and celiac disease. We have advanced in the image analysis classification part of the study, that is based on Artificial Intelligence (CNN and deep learning). Based on conventional H&E staining, we classified using RenNet-based architecture 550 lymphoma subtypes and 1,750,000 image patches.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

The design of the convolutional neural network and optimization of the analysis took some time to design and implement. Several methods were tested. However, we managed to reach a deep learning performance of 99%, which is almost pathologist-human level. Therefore, now we are in position to accelerate the final analyses. Of note, we are experimenting with topology-based AI analysis, which is new type of analysis that we are testing in pilot samples of 150 lymphoma cases.

Strategy for Future Research Activity

The plan is the following: (1) Complete small and quick proof-of-concept projects that we publish in form of preprints and open access journals because we want to get quick feedback from other scientists and society; (2) Deep into the immunohistochemical-based analysis in more "conventional" pathology studies and journals; (3) Complete the deep learning AI-based image classification H&E lymphoma study; (4) Advance in the topology-based AI analysis.

Report

(2 results)
  • 2024 Research-status Report
  • 2023 Research-status Report
  • Research Products

    (39 results)

All 2024 2023 Other

All Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results,  Open Access: 10 results) Presentation (14 results) (of which Invited: 1 results) Remarks (10 results)

  • [Journal Article] Decreased PU.1 expression in mature B cells induces lymphomagenesis2024

    • Author(s)
      Endo Shinya、Nishimura Nao,、Okuno Yutaka、Tatetsu Hiro et al.
    • Journal Title

      Cancer Science

      Volume: 115 Issue: 12 Pages: 3890-3901

    • DOI

      10.1111/cas.16344

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ulcerative Colitis, LAIR1 and TOX2 Expression, and Colorectal Cancer Deep Learning Image Classification Using Convolutional Neural Networks2024

    • Author(s)
      Carreras Joaquim、Roncador Giovanna、Hamoudi Rifat
    • Journal Title

      Cancers

      Volume: 16 Issue: 24 Pages: 4230-4230

    • DOI

      10.3390/cancers16244230

    • Related Report
      2024 Research-status Report
    • Peer Reviewed
  • [Journal Article] Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia2024

    • Author(s)
      Yanagiya R, Miyatake Y, Ando K, Kotani A. et al
    • Journal Title

      Leukemia

      Volume: 38 Issue: 8 Pages: 1731-1741

    • DOI

      10.1038/s41375-024-02296-6

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intrahepatic cholangiocarcinoma with arterial phase hyperenhancement and specialized tumor microenvironment associated with good prognosis after radical resection: A single-center retrospective study2024

    • Author(s)
      Mashiko Taro、Carreras Joaquim、Ogasawara Toshihito、Masuoka Yoshihito、Ei Shigenori、Takahashi Shinichiro、Nomura Takakiyo、Mori Masaki、Koyanagi Kazuo、Yamamoto Seiichiro、Nakamura Naoya、Nakagohri Toshio
    • Journal Title

      Surgery

      Volume: 176 Issue: 2 Pages: 259-266

    • DOI

      10.1016/j.surg.2024.03.024

    • Related Report
      2024 Research-status Report
    • Peer Reviewed
  • [Journal Article] Celiac Disease Deep Learning Image Classification Using Convolutional Neural Networks2024

    • Author(s)
      Carreras Joaquim
    • Journal Title

      Journal of Imaging

      Volume: 10 Issue: 8 Pages: 200-200

    • DOI

      10.3390/jimaging10080200

    • Related Report
      2024 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anomaly Detection and Artificial Intelligence Identified the Pathogenic Role of Apoptosis and RELB Proto-Oncogene, NF-kB Subunit in Diffuse Large B-Cell Lymphoma2024

    • Author(s)
      Carreras Joaquim、Hamoudi Rifat
    • Journal Title

      BioMedInformatics

      Volume: 4 Issue: 2 Pages: 1480-1505

    • DOI

      10.3390/biomedinformatics4020081

    • Related Report
      2024 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unique lipid composition maintained by extracellular blockade leads to prooncogenicity2024

    • Author(s)
      Kai Kudo, Ryo Yanagiya, Masanori Hasegawa, Joaquim Carreras, Yoshimi Miki, Shunya Nakayama, Etsuko Nagashima, Yuji Miyatake, Kan Torii, Kiyoshi Ando, Naoya Nakamura, Akira Miyajima, Makoto Murakami, Ai Kotani
    • Journal Title

      Cell Death Discovery

      Volume: 10 Issue: 1 Pages: 221-231

    • DOI

      10.1038/s41420-024-01971-y

    • Related Report
      2024 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Artificial intelligence and classification of mature lymphoid neoplasms2024

    • Author(s)
      Carreras Joaquim、Hamoudi Rifat、Nakamura Naoya
    • Journal Title

      Exploration of Targeted Anti-tumor Therapy

      Volume: 5 Issue: 2 Pages: 332-348

    • DOI

      10.37349/etat.2024.00221

    • Related Report
      2024 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement2024

    • Author(s)
      Carreras Joaquim、Ikoma Haruka、Kikuti Yara Yukie、Miyaoka Masashi、Hiraiwa Shinichiro、Tomita Sakura、Kondo Yusuke、Ito Atsushi、Nagase Shunsuke、Miura Hisanobu、Kawada Hiroshi、Roncador Giovanna、Campo Elias、Hamoudi Rifat、Nakamura Naoya
    • Journal Title

      Virchows Archiv

      Volume: 484 Issue: 4 Pages: 657-676

    • DOI

      10.1007/s00428-024-03774-z

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Artificial Intelligence, Lymphoid Neoplasms, and Prediction of MYC, BCL2, and BCL6 Gene Expression Using a Pan-Cancer Panel in Diffuse Large B-Cell Lymphoma2024

    • Author(s)
      Carreras Joaquim、Nakamura Naoya
    • Journal Title

      Hemato

      Volume: 5 Issue: 2 Pages: 119-143

    • DOI

      10.3390/hemato5020011

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Artificial Intelligence Analysis and Reverse Engineering of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using Gene Expression Data2024

    • Author(s)
      Carreras Joaquim、Yukie Kikuti Yara、Miyaoka Masashi、Miyahara Saya、Roncador Giovanna、Hamoudi Rifat、Nakamura Naoya
    • Journal Title

      BioMedInformatics

      Volume: 4 Issue: 1 Pages: 295-320

    • DOI

      10.3390/biomedinformatics4010017

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Tumor heterogeneity and immune-evasive T follicular cell lymphoma phenotypes at single-cell resolution2023

    • Author(s)
      Suma Sakurako、Suehara Yasuhito、Fujisawa Manabu、Abe Yoshiaki、Hattori Keiichiro、Sakata-Yanagimoto Mamiko
    • Journal Title

      Leukemia

      Volume: 38 Issue: 2 Pages: 340-350

    • DOI

      10.1038/s41375-023-02093-7

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatic niche leads to aggressive natural killer cell leukemia proliferation through transferrin-transferrin receptor 1 axis2023

    • Author(s)
      Kameda Kazuaki, Yanagiya Ryo, Miyatake Yuji, etal. and Kotani Ai
    • Journal Title

      Blood Journal

      Volume: 142(4) Pages: 352-364

    • DOI

      10.1182/blood.2022018597

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutational Profile and Pathological Features of a Case of Interleukin-10 and RGS1-Positive Spindle Cell Variant Diffuse Large B-Cell Lymphoma2023

    • Author(s)
      Carreras Joaquim、Kikuti Yara Yukie、Miyaoka Masashi、Hiraiwa Shinichiro、Tomita Sakura、Ikoma Haruka、Kondo Yusuke、Ito Atsushi、Nagase Shunsuke、Miura Hisanobu、Roncador Giovanna、Colomo Lluis、Hamoudi Rifat、Campo Elias、Nakamura Naoya
    • Journal Title

      Hematology Reports

      Volume: 15 Issue: 1 Pages: 188-200

    • DOI

      10.3390/hematolrep15010020

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The pathobiology of follicular lymphoma2023

    • Author(s)
      Carreras Joaquim
    • Journal Title

      Journal of Clinical and Experimental Hematopathology

      Volume: 63 Issue: 3 Pages: 152-163

    • DOI

      10.3960/jslrt.23014

    • ISSN
      1346-4280, 1880-9952
    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Actionable immuno-oncology markers in the microenvironment of monomorphic epitheliotropic intestinal T-cell lymphoma2024

    • Author(s)
      Carreras Joaquim
    • Organizer
      第114回日本病理学会総会
    • Related Report
      2024 Research-status Report
  • [Presentation] Clinicopathological analysis and reclassification of EBV+LBCL including DLBCL and Hodgkin lymphoma2024

    • Author(s)
      Shunsuke Nagase, Carreras Joaquim
    • Organizer
      第114回日本病理学会総会
    • Related Report
      2024 Research-status Report
  • [Presentation] TP53 analysis of acanthotic squamous epithelium of undetermined significance in oral cavity2024

    • Author(s)
      Yusuke Kondo, Carreras Joaquim
    • Organizer
      第114回日本病理学会総会
    • Related Report
      2024 Research-status Report
  • [Presentation] A case of severe hematopoietic and multiple organ failure after CAR-T cell therapy for myeloma2024

    • Author(s)
      Atsushi Ito, Carreras Joaquim
    • Organizer
      第114回日本病理学会総会
    • Related Report
      2024 Research-status Report
  • [Presentation] 濾胞樹状細胞肉腫:分類の現状2024

    • Author(s)
      長瀬 駿介,松岡 亮太,菊池 イアーラ幸江,カレーラス ジュアキム , 中村 直哉
    • Organizer
      第64回日本リンパ網内系学会学術集会・総会
    • Related Report
      2024 Research-status Report
  • [Presentation] High grade B-cell lymphoma with MYC and BCL2 and/or BCL6-rearrangements (WHO revised 4th) 101例の臨床病理学的,遺伝子学的解析2024

    • Author(s)
      宮岡 雅,菊地イアーラ 幸江,カレーラス ジュアキム,中村 直哉
    • Organizer
      第64回日本リンパ網内系学会学術集会・総会
    • Related Report
      2024 Research-status Report
  • [Presentation] EBV陽性DLBCLとEBV陽性Hodgkinリンパ腫の臨床病理学的・遺伝子学的検討2024

    • Author(s)
      長瀬 駿介,菊池 イアーラ幸江,カレーラス ジュアキム ,川田 浩志, 中村 直哉
    • Organizer
      第64回日本リンパ網内系学会学術集会・総会
    • Related Report
      2024 Research-status Report
  • [Presentation] P-37 びまん性大細胞型B細胞リンパ腫における異常検出分析とNF-KB RELB Protooncogene発現2024

    • Author(s)
      カレーラス ジュアキム,菊池 イアーラ,宮岡 雅,冨; さくら,駒 悠, 近藤 裕介,伊藤 淳史,長瀬 駿介, ロンカドル ギオバンナ,リファット ハモウヂ,中村 直哉
    • Organizer
      第64回日本リンパ網内系学会学術集会・総会
    • Related Report
      2024 Research-status Report
  • [Presentation] My research life in Japan2024

    • Author(s)
      Carreras Joaquim
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] Gene expression and mutational profile of PD-L1 positive diffuse large B-cel l lymphoma2024

    • Author(s)
      Carreras Joaquim
    • Organizer
      第113回日本病理学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] High Expression of Caspase-8 Associated with Improved Survival in Diffuse Large B-Cell Lymphoma2023

    • Author(s)
      Carreras Joaquim
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] P-44. High PD-L1 expression correlated with poor prognosis of diffuse large B-cell lymphoma2023

    • Author(s)
      Carreras Joaquim
    • Organizer
      第63回日本リンパ網内系学会学術集会・総会
    • Related Report
      2023 Research-status Report
  • [Presentation] P-66. Surface CD3陰性Monomorphic epitheliotropic intestinal T-cell lymphoma 3例の遺伝子変異解析2023

    • Author(s)
      冨田さくら, Joaquim Carreras, 菊池イアーラ幸江, 堂本英治, Edoardo Missiaglia, Justine Bouilly, Andrey Leourneau, Laurence de Leval
    • Organizer
      第63回日本リンパ網内系学会学術集会・総会
    • Related Report
      2023 Research-status Report
  • [Presentation] P-68. Nodal marginal zone lymphomaの遺伝子発現解析2023

    • Author(s)
      生駒悠, Carreras Joaquim, 菊池イアーラ幸江, 中村直哉
    • Organizer
      第63回日本リンパ網内系学会学術集会・総会
    • Related Report
      2023 Research-status Report
  • [Remarks] ORCID Joaquim Carreras

    • URL

      https://orcid.org/0000-0002-6129-8299

    • Related Report
      2024 Research-status Report
  • [Remarks] Loop Joaquim Carreras

    • URL

      https://loop.frontiersin.org/people/956781/overview

    • Related Report
      2024 Research-status Report
  • [Remarks] Scilit Joaquim Carreras

    • URL

      https://sciprofiles.com/profile/joaquim_carreras

    • Related Report
      2024 Research-status Report
  • [Remarks] Researchgate Joaquim Carreras

    • URL

      https://www.researchgate.net/profile/Joaquim_Carreras

    • Related Report
      2024 Research-status Report
  • [Remarks] Tokai University Website

    • URL

      http://carreras.med.u-tokai.ac.jp/

    • Related Report
      2024 Research-status Report
  • [Remarks] Research Activities of Joaquim Carreras

    • URL

      http://carreras.med.u-tokai.ac.jp/

    • Related Report
      2023 Research-status Report
  • [Remarks] ORCID

    • URL

      https://orcid.org/0000-0002-6129-8299

    • Related Report
      2023 Research-status Report
  • [Remarks] Researchgate of Joaquim Carreras

    • URL

      https://www.researchgate.net/profile/Joaquim-Carreras

    • Related Report
      2023 Research-status Report
  • [Remarks] Loop Joaquim Carreras

    • URL

      https://loop.frontiersin.org/people/956781/publications

    • Related Report
      2023 Research-status Report
  • [Remarks] Scilit Joaquim Carreras

    • URL

      https://www.scilit.net/scholars/9538763

    • Related Report
      2023 Research-status Report

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Published: 2023-04-13   Modified: 2025-12-26  

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