Addressing the Challenges of High‐Throughput Cancer Tissue Proteomics for Clinical Application: ProCan

The cancer tissue proteome has enormous potential as a source of novel predictive biomarkers in oncology. Progress in the development of mass spectrometry (MS)‐based tissue proteomics now presents an opportunity to exploit this by applying the strategies of comprehensive molecular profiling and big‐data analytics that are refined in other fields of ‘omics research. ProCan (ProCan is a registered trademark) is a program aiming to generate high‐quality tissue proteomic data across a broad spectrum of cancer types. It is based on data‐independent acquisition–MS proteomic analysis of annotated tissue samples sourced through collaboration with expert clinical and cancer research groups. The practical requirements of a high‐throughput translational research program have shaped the approach that ProCan is taking to address challenges in study design, sample preparation, raw data acquisition, and data analysis. The ultimate goal is to establish a large proteomics knowledge‐base that, in combination with other cancer ‘omics data, will accelerate cancer research.     

机器学习在微生物组宿主表型预测中的应用

随着大数据时代的到来,如何将生物组学海量数据转化为易理解及可视化的知识是当前生物信息学面临的重要挑战之一。为了处理复杂、高维的微生物组数据,目前机器学习算法已被应用于人体微生物组研究,以揭示疾病背后的复杂机制。本文首先简述了微生物组数据处理方法及常用的机器学习算法,如支持向量机(SVM)、随机森林(RF)和人工神经网络(ANN)等,然后对机器学习的工作流程及其要点进行阐述,并探讨了机器学习算法在基于微生物组数据预测宿主表型方面的应用。最后以唾液微生物组数据预测口腔异味为例,实现了机器学习算法的模型构建与评估分析,并提供了可用于微生物组研究实践的R/Python代码(https://github.com/LiLabZSU/microbioML)。     

AI applications to medical images: From machine learning to deep learning

PurposeArtificial intelligence (AI) models are playing an increasing role in biomedical research and healthcare services. This review focuses on challenges points to be clarified about how to develop AI applications as clinical decision support systems in the real-world context.MethodsA narrative review has been performed including a critical assessment of articles published between 1989 and 2021 that guided challenging sections.ResultsWe first illustrate the architectural characteristics of machine learning (ML)/radiomics and deep learning (DL) approaches. For ML/radiomics, the phases of feature selection and of training, validation, and testing are described. DL models are presented as multi-layered artificial/convolutional neural networks, allowing us to directly process images. The data curation section includes technical steps such as image labelling, image annotation (with segmentation as a crucial step in radiomics), data harmonization (enabling compensation for differences in imaging protocols that typically generate noise in non-AI imaging studies) and federated learning. Thereafter, we dedicate specific sections to: sample size calculation, considering multiple testing in AI approaches; procedures for data augmentation to work with limited and unbalanced datasets; and the interpretability of AI models (the so-called black box issue). Pros and cons for choosing ML versus DL to implement AI applications to medical imaging are finally presented in a synoptic way.ConclusionsBiomedicine and healthcare systems are one of the most important fields for AI applications and medical imaging is probably the most suitable and promising domain. Clarification of specific challenging points facilitates the development of such systems and their translation to clinical practice.     

Radiomics in radiooncology – Challenging the medical physicist

PurposeNoticing the fast growing translation of artificial intelligence (AI) technologies to medical image analysis this paper emphasizes the future role of the medical physicist in this evolving field. Specific challenges are addressed when implementing big data concepts with high-throughput image data processing like radiomics and machine learning in a radiooncology environment to support clinical decisions.MethodsBased on the experience of our interdisciplinary radiomics working group, techniques for processing minable data, extracting radiomics features and associating this information with clinical, physical and biological data for the development of prediction models are described. A special emphasis was placed on the potential clinical significance of such an approach.ResultsClinical studies demonstrate the role of radiomics analysis as an additional independent source of information with the potential to influence the radiooncology practice, i.e. to predict patient prognosis, treatment response and underlying genetic changes. Extending the radiomics approach to integrate imaging, clinical, genetic and dosimetric data (‘panomics’) challenges the medical physicist as member of the radiooncology team.ConclusionsThe new field of big data processing in radiooncology offers opportunities to support clinical decisions, to improve predicting treatment outcome and to stimulate fundamental research on radiation response both of tumor and normal tissue. The integration of physical data (e.g. treatment planning, dosimetric, image guidance data) demands an involvement of the medical physicist in the radiomics approach of radiooncology. To cope with this challenge national and international organizations for medical physics should organize more training opportunities in artificial intelligence technologies in radiooncology.     

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy

PurposeTo perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results.Materials and MethodsA Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015–2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging.ResultsThe Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019.ConclusionsWe are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.     

Evaluation and comparison of multi-omics data integration methods for cancer subtyping

Computational integrative analysis has become a significant approach in the data-driven exploration of biological problems. Many integration methods for cancer subtyping have been proposed, but evaluating these methods has become a complicated problem due to the lack of gold standards. Moreover, questions of practical importance remain to be addressed regarding the impact of selecting appropriate data types and combinations on the performance of integrative studies. Here, we constructed three classes of benchmarking datasets of nine cancers in TCGA by considering all the eleven combinations of four multi-omics data types. Using these datasets, we conducted a comprehensive evaluation of ten representative integration methods for cancer subtyping in terms of accuracy measured by combining both clustering accuracy and clinical significance, robustness, and computational efficiency. We subsequently investigated the influence of different omics data on cancer subtyping and the effectiveness of their combinations. Refuting the widely held intuition that incorporating more types of omics data always produces better results, our analyses showed that there are situations where integrating more omics data negatively impacts the performance of integration methods. Our analyses also suggested several effective combinations for most cancers under our studies, which may be of particular interest to researchers in omics data analysis.     

Artificial intelligence in the diagnosis of COVID-19: challenges and perspectives

Artificial intelligence (AI) is being used to aid in various aspects of the COVID-19 crisis, including epidemiology, molecular research and drug development, medical diagnosis and treatment, and socioeconomics. The association of AI and COVID-19 can accelerate to rapidly diagnose positive patients. To learn the dynamics of a pandemic with relevance to AI, we search the literature using the different academic databases (PubMed, PubMed Central, Scopus, Google Scholar) and preprint servers (bioRxiv, medRxiv, arXiv). In the present review, we address the clinical applications of machine learning and deep learning, including clinical characteristics, electronic medical records, medical images (CT, X-ray, ultrasound images, etc.) in the COVID-19 diagnosis. The current challenges and future perspectives provided in this review can be used to direct an ideal deployment of AI technology in a pandemic.     

Artificial intelligence in radiotherapy

Artificial intelligence (AI) has already been implemented widely in the medical field in the recent years. This paper first reviews the background of AI and radiotherapy. Then it explores the basic concepts of different AI algorithms and machine learning methods, such as neural networks, that are available to us today and how they are being implemented in radiotherapy and diagnostic processes, such as medical imaging, treatment planning, patient simulation, quality assurance and radiation dose delivery. It also explores the ongoing research on AI methods that are to be implemented in radiotherapy in the future. The review shows very promising progress and future for AI to be widely used in various areas of radiotherapy. However, basing on various concerns such as availability and security of using big data, and further work on polishing and testing AI algorithms, it is found that we may not ready to use AI primarily in radiotherapy at the moment.     

Multiomics metabolic and epigenetics regulatory network in cancer: A systems biology perspective

Genetic, epigenetic, and metabolic alterations are all hallmarks of cancer. However, the epigenome and metabolome are both highly complex and dynamic biological networks in vivo. The interplay between the epigenome and metabolome contributes to a biological system that is responsive to the tumor microenvironment and possesses a wealth of unknown biomarkers and targets of cancer therapy. From this perspective, we first review the state of high-throughput biological data acquisition(i.e. multiomics data)and analysis(i.e. computational tools) and then propose a conceptual in silico metabolic and epigenetic regulatory network(MER-Net) that is based on these current high-throughput methods. The conceptual MER-Net is aimed at linking metabolomic and epigenomic networks through observation of biological processes, omics data acquisition, analysis of network information, and integration with validated database knowledge. Thus, MER-Net could be used to reveal new potential biomarkers and therapeutic targets using deep learning models to integrate and analyze large multiomics networks. We propose that MER-Net can serve as a tool to guide integrated metabolomics and epigenomics research or can be modified to answer other complex biological and clinical questions using multiomics data.     

基于深度学习的作物基因组学和遗传改良

随着世界人口的不断增长、食物需求量的不断增加,以及气候的不断变化,如何提高农作物产量已成为人类面临的一个巨大挑战。传统设计育种耗时长、效率低,已经不能满足新时代的育种需求。随着基因型和表型数据成本的不断降低,以及各种组学数据的爆炸式增长,人工智能技术作为能够在大数据中高效率挖掘信息的工具,在生物学领域受到了广泛关注。人工智能指导的设计育种将大大加快育种的效率,给育种带来革命性的变化。介绍了人工智能特别是深度学习在作物基因组学和遗传改良中的应用,并进行了总结与展望,以期为智能设计育种提供新的思路。     

AggMapNet: enhanced and explainable low-sample omics deep learning with feature-aggregated multi-channel networks

Omics-based biomedical learning frequently relies on data of high-dimensions (up to thousands) and low-sample sizes (dozens to hundreds), which challenges efficient deep learning (DL) algorithms, particularly for low-sample omics investigations. Here, an unsupervised novel feature aggregation tool AggMap was developed to Aggregate and Map omics features into multi-channel 2D spatial-correlated image-like feature maps (Fmaps) based on their intrinsic correlations. AggMap exhibits strong feature reconstruction capabilities on a randomized benchmark dataset, outperforming existing methods. With AggMap multi-channel Fmaps as inputs, newly-developed multi-channel DL AggMapNet models outperformed the state-of-the-art machine learning models on 18 low-sample omics benchmark tasks. AggMapNet exhibited better robustness in learning noisy data and disease classification. The AggMapNet explainable module Simply-explainer identified key metabolites and proteins for COVID-19 detections and severity predictions. The unsupervised AggMap algorithm of good feature restructuring abilities combined with supervised explainable AggMapNet architecture establish a pipeline for enhanced learning and interpretability of low-sample omics data.     

Large-scale pharmacogenomic studies and drug response prediction for personalized cancer medicine

The response rate of most anti-cancer drugs is limited because of the high heterogeneity of cancer and the complex mechanism of drug action. Personalized treatment that stratifies patients into subgroups using molecular biomarkers is promising to improve clinical benefit. With the accumulation of preclinical models and advances in computational approaches of drug response prediction, pharmacogenomics has made great success over the last 20 years and is increasingly used in the clinical practice of personalized cancer medicine. In this article, we first summarize FDA-approved pharmacogenomic biomarkers and large-scale pharmacogenomic studies of preclinical cancer models such as patient-derived cell lines, organoids, and xenografts. Furthermore, we comprehensively review the recent developments of computational methods in drug response prediction, covering network, machine learning, and deep learning technologies and strategies to evaluate immunotherapy response. In the end, we discuss challenges and propose possible solutions for further improvement.     

Ancient genes can be served as pan‐cancer diagnostic and prognostic biomarkers

One important challenge for cancer is efficient biomarkers monitoring its formation and developments remain greatly limited. Although the accumulated big omics data provide great opportunities to the above purpose, the biomarkers identified by the data‐driven strategy often do not work well in new datasets, which is one of the main bottlenecks limiting their utilities. Given that atavistic phenotype is generally observed in cancer cells, we have been suggested that the activity of progenitor genes in tumour could serve as an efficient cancer biomarker. For doing so, we first curated 77 progenitor genes and then proposed a quantitative score to evaluate cancer progenitorness. After applying progenitorness score to ~ 22 000 samples, 33 types of cancers from 81 datasets, this method generally performs well in the diagnosis, prognosis and therapy monitoring of cancers. This study proposed a potential pan‐cancer biomarker and revealed a significant role of atavism in the formation and development of cancers.     

Application of radiomics and machine learning in head and neck cancers

With the continuous development of medical image informatics technology, more and more high-throughput quantitative data could be extracted from digital medical images, which has resulted in a new kind of omics-Radiomics. In recent years, in addition to genomics, proteomics and metabolomics, radiomic has attracted the interest of more and more researchers. Compared to other omics, radiomics can be perfectly integrated with clinical data, even with the pathology and molecular biomarker, so that the study can be closer to the clinical reality and more revealing of the tumor development. Mass data will also be generated in this process. Machine learning, due to its own characteristics, has a unique advantage in processing massive radiomic data. By analyzing mass amounts of data with strong clinical relevance, people can construct models that more accurately reflect tumor development and progression, thereby providing the possibility of personalized and sequential treatment of patients. As one of the cancer types whose treatment and diagnosis rely on imaging examination, radiomics has a very broad application prospect in head and neck cancers (HNC). Until now, there have been some notable results in HNC. In this review, we will introduce the concepts and workflow of radiomics and machine learning and their current applications in head and neck cancers, as well as the directions and applications of artificial intelligence in the treatment and diagnosis of HNC.     

Artificial intelligence and machine learning for medical imaging: A technology review

Artificial intelligence (AI) has recently become a very popular buzzword, as a consequence of disruptive technical advances and impressive experimental results, notably in the field of image analysis and processing. In medicine, specialties where images are central, like radiology, pathology or oncology, have seized the opportunity and considerable efforts in research and development have been deployed to transfer the potential of AI to clinical applications. With AI becoming a more mainstream tool for typical medical imaging analysis tasks, such as diagnosis, segmentation, or classification, the key for a safe and efficient use of clinical AI applications relies, in part, on informed practitioners. The aim of this review is to present the basic technological pillars of AI, together with the state-of-the-art machine learning methods and their application to medical imaging. In addition, we discuss the new trends and future research directions. This will help the reader to understand how AI methods are now becoming an ubiquitous tool in any medical image analysis workflow and pave the way for the clinical implementation of AI-based solutions.     

Outcome modeling techniques for prostate cancer radiotherapy: Data,models, and validation

Prostate cancer is a frequently diagnosed malignancy worldwide and radiation therapy is a first-line approach in treating localized as well as locally advanced cases. The limiting factor in modern radiotherapy regimens is dose to normal structures, an excess of which can lead to aberrant radiation-induced toxicities. Conversely, dose reduction to spare adjacent normal structures risks underdosing target volumes and compromising local control. As a result, efforts aimed at predicting the effects of radiotherapy could invaluably optimize patient treatments by mitigating such toxicities and simultaneously maximizing biochemical control. In this work, we review the types of data, frameworks and techniques used for prostate radiotherapy outcome modeling. Consideration is given to clinical and dose-volume metrics, such as those amassed by the QUANTEC initiative, and also to newer methods for the integration of biological and genetic factors to improve prediction performance. We furthermore highlight trends in machine learning that may help to elucidate the complex pathophysiological mechanisms of tumor control and radiation-induced normal tissue side effects.     

Interaction of IGF signaling and the androgen receptor in prostate cancer progression

The insulin-like growth factor type I receptor (IGF-IR) has been suggested to play an important role in prostate cancer progression and possibly in the progression to androgen-independent (AI) disease. The term AI may not be entirely correct, in that recent data suggest that expression of androgen receptor (AR) and androgen-regulated genes is the primary association with prostate cancer progression after hormone ablation. Therefore, signaling through other growth factors has been thought to play a role in AR-mediated prostate cancer progression to AI disease in the absence of androgen ligand. However, existing data on how IGF-IR signaling interacts with AR activation in prostate cancer are conflicting. In this Prospect article, we review some of the published data on the mechanisms of IGF-IR/AR interaction and present new evidence that IGF-IR signaling may modulate AR compartmentation and thus alter AR activity in prostate cancer cells. Inhibition of IGF-IR signaling can result in cytoplasmic AR retention and a significant change in androgen-regulated gene expression. Translocation of AR from the cytoplasm to the nucleus may be associated with IGF-induced dephosphorylation. Since fully humanized antibodies targeting the IGF-IR are now in clinical trials, the current review is intended to reveal the mechanisms of potential therapeutic effects of these antibodies on AI prostate cancers.