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1. The Temple University Digital Pathology Corpus: The Breast Tissue Subset

   https://doi.org/10.1109/SPMB52430.2021.9672275  

   Wevodau, Z. ; Doshna, B. ; Jhala, N. ; Akhtar, I. ; Obeid, I. ; Picone, J. ( December 2021 , Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   Obeid, I. (Ed.)

   The Neural Engineering Data Consortium (NEDC) is developing the Temple University Digital Pathology Corpus (TUDP), an open source database of high-resolution images from scanned pathology samples [1], as part of its National Science Foundation-funded Major Research Instrumentation grant titled “MRI: High Performance Digital Pathology Using Big Data and Machine Learning” [2]. The long-term goal of this project is to release one million images. We have currently scanned over 100,000 images and are in the process of annotating breast tissue data for our first official corpus release, v1.0.0. This release contains 3,505 annotated images of breast tissue including 74 patients with cancerous diagnoses (out of a total of 296 patients). In this poster, we will present an analysis of this corpus and discuss the challenges we have faced in efficiently producing high quality annotations of breast tissue. It is well known that state of the art algorithms in machine learning require vast amounts of data. Fields such as speech recognition [3], image recognition [4] and text processing [5] are able to deliver impressive performance with complex deep learning models because they have developed large corpora to support training of extremely high-dimensional models (e.g., billions of parameters). Other fields that do not have access to such data resources must rely on techniques in which existing models can be adapted to new datasets [6]. A preliminary version of this breast corpus release was tested in a pilot study using a baseline machine learning system, ResNet18 [7], that leverages several open-source Python tools. The pilot corpus was divided into three sets: train, development, and evaluation. Portions of these slides were manually annotated [1] using the nine labels in Table 1 [8] to identify five to ten examples of pathological features on each slide. Not every pathological feature is annotated, meaning excluded areas can include focuses particular to these labels that are not used for training. A summary of the number of patches within each label is given in Table 2. To maintain a balanced training set, 1,000 patches of each label were used to train the machine learning model. Throughout all sets, only annotated patches were involved in model development. The performance of this model in identifying all the patches in the evaluation set can be seen in the confusion matrix of classification accuracy in Table 3. The highest performing labels were background, 97% correct identification, and artifact, 76% correct identification. A correlation exists between labels with more than 6,000 development patches and accurate performance on the evaluation set. Additionally, these results indicated a need to further refine the annotation of invasive ductal carcinoma (“indc”), inflammation (“infl”), nonneoplastic features (“nneo”), normal (“norm”) and suspicious (“susp”). This pilot experiment motivated changes to the corpus that will be discussed in detail in this poster presentation. To increase the accuracy of the machine learning model, we modified how we addressed underperforming labels. One common source of error arose with how non-background labels were converted into patches. Large areas of background within other labels were isolated within a patch resulting in connective tissue misrepresenting a non-background label. In response, the annotation overlay margins were revised to exclude benign connective tissue in non-background labels. Corresponding patient reports and supporting immunohistochemical stains further guided annotation reviews. The microscopic diagnoses given by the primary pathologist in these reports detail the pathological findings within each tissue site, but not within each specific slide. The microscopic diagnoses informed revisions specifically targeting annotated regions classified as cancerous, ensuring that the labels “indc” and “dcis” were used only in situations where a micropathologist diagnosed it as such. Further differentiation of cancerous and precancerous labels, as well as the location of their focus on a slide, could be accomplished with supplemental immunohistochemically (IHC) stained slides. When distinguishing whether a focus is a nonneoplastic feature versus a cancerous growth, pathologists employ antigen targeting stains to the tissue in question to confirm the diagnosis. For example, a nonneoplastic feature of usual ductal hyperplasia will display diffuse staining for cytokeratin 5 (CK5) and no diffuse staining for estrogen receptor (ER), while a cancerous growth of ductal carcinoma in situ will have negative or focally positive staining for CK5 and diffuse staining for ER [9]. Many tissue samples contain cancerous and non-cancerous features with morphological overlaps that cause variability between annotators. The informative fields IHC slides provide could play an integral role in machine model pathology diagnostics. Following the revisions made on all the annotations, a second experiment was run using ResNet18. Compared to the pilot study, an increase of model prediction accuracy was seen for the labels indc, infl, nneo, norm, and null. This increase is correlated with an increase in annotated area and annotation accuracy. Model performance in identifying the suspicious label decreased by 25% due to the decrease of 57% in the total annotated area described by this label. A summary of the model performance is given in Table 4, which shows the new prediction accuracy and the absolute change in error rate compared to Table 3. The breast tissue subset we are developing includes 3,505 annotated breast pathology slides from 296 patients. The average size of a scanned SVS file is 363 MB. The annotations are stored in an XML format. A CSV version of the annotation file is also available which provides a flat, or simple, annotation that is easy for machine learning researchers to access and interface to their systems. Each patient is identified by an anonymized medical reference number. Within each patient’s directory, one or more sessions are identified, also anonymized to the first of the month in which the sample was taken. These sessions are broken into groupings of tissue taken on that date (in this case, breast tissue). A deidentified patient report stored as a flat text file is also available. Within these slides there are a total of 16,971 total annotated regions with an average of 4.84 annotations per slide. Among those annotations, 8,035 are non-cancerous (normal, background, null, and artifact,) 6,222 are carcinogenic signs (inflammation, nonneoplastic and suspicious,) and 2,714 are cancerous labels (ductal carcinoma in situ and invasive ductal carcinoma in situ.) The individual patients are split up into three sets: train, development, and evaluation. Of the 74 cancerous patients, 20 were allotted for both the development and evaluation sets, while the remain 34 were allotted for train. The remaining 222 patients were split up to preserve the overall distribution of labels within the corpus. This was done in hope of creating control sets for comparable studies. Overall, the development and evaluation sets each have 80 patients, while the training set has 136 patients. In a related component of this project, slides from the Fox Chase Cancer Center (FCCC) Biosample Repository (https://www.foxchase.org/research/facilities/genetic-research-facilities/biosample-repository -facility) are being digitized in addition to slides provided by Temple University Hospital. This data includes 18 different types of tissue including approximately 38.5% urinary tissue and 16.5% gynecological tissue. These slides and the metadata provided with them are already anonymized and include diagnoses in a spreadsheet with sample and patient ID. We plan to release over 13,000 unannotated slides from the FCCC Corpus simultaneously with v1.0.0 of TUDP. Details of this release will also be discussed in this poster. Few digitally annotated databases of pathology samples like TUDP exist due to the extensive data collection and processing required. The breast corpus subset should be released by November 2021. By December 2021 we should also release the unannotated FCCC data. We are currently annotating urinary tract data as well. We expect to release about 5,600 processed TUH slides in this subset. We have an additional 53,000 unprocessed TUH slides digitized. Corpora of this size will stimulate the development of a new generation of deep learning technology. In clinical settings where resources are limited, an assistive diagnoses model could support pathologists’ workload and even help prioritize suspected cancerous cases. ACKNOWLEDGMENTS This material is supported by the National Science Foundation under grants nos. CNS-1726188 and 1925494. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. REFERENCES [1] N. Shawki et al., “The Temple University Digital Pathology Corpus,” in Signal Processing in Medicine and Biology: Emerging Trends in Research and Applications, 1st ed., I. Obeid, I. Selesnick, and J. Picone, Eds. New York City, New York, USA: Springer, 2020, pp. 67 104. https://www.springer.com/gp/book/9783030368432. [2] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning.” Major Research Instrumentation (MRI), Division of Computer and Network Systems, Award No. 1726188, January 1, 2018 – December 31, 2021. https://www. isip.piconepress.com/projects/nsf_dpath/. [3] A. Gulati et al., “Conformer: Convolution-augmented Transformer for Speech Recognition,” in Proceedings of the Annual Conference of the International Speech Communication Association (INTERSPEECH), 2020, pp. 5036-5040. https://doi.org/10.21437/interspeech.2020-3015. [4] C.-J. Wu et al., “Machine Learning at Facebook: Understanding Inference at the Edge,” in Proceedings of the IEEE International Symposium on High Performance Computer Architecture (HPCA), 2019, pp. 331–344. https://ieeexplore.ieee.org/document/8675201. [5] I. Caswell and B. Liang, “Recent Advances in Google Translate,” Google AI Blog: The latest from Google Research, 2020. [Online]. Available: https://ai.googleblog.com/2020/06/recent-advances-in-google-translate.html. [Accessed: 01-Aug-2021]. [6] V. Khalkhali, N. Shawki, V. Shah, M. Golmohammadi, I. Obeid, and J. Picone, “Low Latency Real-Time Seizure Detection Using Transfer Deep Learning,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2021, pp. 1 7. https://www.isip. piconepress.com/publications/conference_proceedings/2021/ieee_spmb/eeg_transfer_learning/. [7] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning,” Philadelphia, Pennsylvania, USA, 2020. https://www.isip.piconepress.com/publications/reports/2020/nsf/mri_dpath/. [8] I. Hunt, S. Husain, J. Simons, I. Obeid, and J. Picone, “Recent Advances in the Temple University Digital Pathology Corpus,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2019, pp. 1–4. https://ieeexplore.ieee.org/document/9037859. [9] A. P. Martinez, C. Cohen, K. Z. Hanley, and X. (Bill) Li, “Estrogen Receptor and Cytokeratin 5 Are Reliable Markers to Separate Usual Ductal Hyperplasia From Atypical Ductal Hyperplasia and Low-Grade Ductal Carcinoma In Situ,” Arch. Pathol. Lab. Med., vol. 140, no. 7, pp. 686–689, Apr. 2016. https://doi.org/10.5858/arpa.2015-0238-OA. 

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2. Improving natural language information extraction from cancer pathology reports using transfer learning and zero-shot string similarity

   https://doi.org/10.1093/jamiaopen/ooab085  

   Park, Briton ; Altieri, Nicholas ; DeNero, John ; Odisho, Anobel Y ; Yu, Bin ( July 2021 , JAMIA Open)

   Abstract Objective We develop natural language processing (NLP) methods capable of accurately classifying tumor attributes from pathology reports given minimal labeled examples. Our hierarchical cancer to cancer transfer (HCTC) and zero-shot string similarity (ZSS) methods are designed to exploit shared information between cancers and auxiliary class features, respectively, to boost performance using enriched annotations which give both location-based information and document level labels for each pathology report. Materials and Methods Our data consists of 250 pathology reports each for kidney, colon, and lung cancer from 2002 to 2019 from a single institution (UCSF). For each report, we classified 5 attributes: procedure, tumor location, histology, grade, and presence of lymphovascular invasion. We develop novel NLP techniques involving transfer learning and string similarity trained on enriched annotations. We compare HCTC and ZSS methods to the state-of-the-art including conventional machine learning methods as well as deep learning methods. Results For our HCTC method, we see an improvement of up to 0.1 micro-F1 score and 0.04 macro-F1 averaged across cancer and applicable attributes. For our ZSS method, we see an improvement of up to 0.26 micro-F1 and 0.23 macro-F1 averaged across cancer and applicable attributes. These comparisons are made after adjusting training data sizes to correct for the 20% increase in annotation time for enriched annotations compared to ordinary annotations. Conclusions Methods based on transfer learning across cancers and augmenting information methods with string similarity priors can significantly reduce the amount of labeled data needed for accurate information extraction from pathology reports. 

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3. VERB: Visualizing and Interpreting Bias Mitigation Techniques Geometrically for Word Representations

   Rathore, Archit ; Dev, Sunipa ; Phillips, Jeff M. ; Srikumar, Vivek ; Zheng, Yan ; Yeh, Chin-Chia Michael ; Wang, Junpeng ; Zhang, Wei ; Wang, Bei ( June 2023 , ACM Transactions on Interactive Intelligent Systems)

   Word vector embeddings have been shown to contain and amplify biases in the data they are extracted from. Consequently, many techniques have been proposed to identify, mitigate, and attenuate these biases in word representations. In this paper, we utilize interactive visualization to increase the interpretability and accessibility of a collection of state-of-the-art debiasing techniques. To aid this, we present the Visualization of Embedding Representations for deBiasing (“VERB”) system, an open-source web-based visualization tool that helps users gain a technical understanding and visual intuition of the inner workings of debiasing techniques, with a focus on their geometric properties. In particular, VERB offers easy-to-follow examples that explore the effects of these debiasing techniques on the geometry of high-dimensional word vectors. To help understand how various debiasing techniques change the underlying geometry, VERB decomposes each technique into interpretable sequences of primitive transformations and highlights their effect on the word vectors using dimensionality reduction and interactive visual exploration. VERB is designed to target natural language processing (NLP) practitioners who are designing decision-making systems on top of word embeddings, and also researchers working with the fairness and ethics of machine learning systems in NLP. It can also serve as a visual medium for education, which helps an NLP novice understand and mitigate biases in word embeddings. 

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4. VERB: Visualizing and Interpreting Bias Mitigation Techniques Geometrically for Word Representations

   Rathore, Archit ; Dev, Sunipa ; Phillips, Jeff M. ; Srikumar, Vivek ; Zheng, Yan ; Yeh, Chin-Chia Michael ; Wang, Junpeng ; Zhang, Wei ; Wang, Bei ( January 2024 , ACM transactions on interactive intelligent systems)

   Word vector embeddings have been shown to contain and amplify biases in the data they are extracted from. Consequently, many techniques have been proposed to identify, mitigate, and attenuate these biases in word representations. In this paper, we utilize interactive visualization to increase the interpretability and accessibility of a collection of state-of-the-art debiasing techniques. To aid this, we present the Visualization of Embedding Representations for deBiasing (“VERB”) system, an open-source web-based visualization tool that helps users gain a technical understanding and visual intuition of the inner workings of debiasing techniques, with a focus on their geometric properties. In particular, VERB offers easy-to-follow examples that explore the effects of these debiasing techniques on the geometry of high-dimensional word vectors. To help understand how various debiasing techniques change the underlying geometry, VERB decomposes each technique into interpretable sequences of primitive transformations and highlights their effect on the word vectors using dimensionality reduction and interactive visual exploration. VERB is designed to target natural language processing (NLP) practitioners who are designing decision-making systems on top of word embeddings, and also researchers working with the fairness and ethics of machine learning systems in NLP. It can also serve as a visual medium for education, which helps an NLP novice understand and mitigate biases in word embeddings. 

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5. Plant Science Knowledge Graph Corpus: a gold standard entity and relation corpus for the molecular plant sciences

   https://doi.org/10.1093/insilicoplants/diad021  

   Lotreck, Serena ; Segura Abá, Kenia ; Lehti-Shiu, Melissa D. ; Seeger, Abigail ; Brown, Brianna N. I. ; Ranaweera, Thilanka ; Schumacher, Ally ; Ghassemi, Mohammad ; Shiu, Shin-Han ; Marshall-Colon, ed., Amy ( November 2023 , in silico Plants)

   Natural language processing (NLP) techniques can enhance our ability to interpret plant science literature. Many state-of-the-art algorithms for NLP tasks require high-quality labelled data in the target domain, in which entities like genes and proteins, as well as the relationships between entities, are labelled according to a set of annotation guidelines. While there exist such datasets for other domains, these resources need development in the plant sciences. Here, we present the Plant ScIenCe KnowLedgE Graph (PICKLE) corpus, a collection of 250 plant science abstracts annotated with entities and relations, along with its annotation guidelines. The annotation guidelines were refined by iterative rounds of overlapping annotations, in which inter-annotator agreement was leveraged to improve the guidelines. To demonstrate PICKLE’s utility, we evaluated the performance of pretrained models from other domains and trained a new, PICKLE-based model for entity and relation extraction (RE). The PICKLE-trained models exhibit the second-highest in-domain entity performance of all models evaluated, as well as a RE performance that is on par with other models. Additionally, we found that computer science-domain models outperformed models trained on a biomedical corpus (GENIA) in entity extraction, which was unexpected given the intuition that biomedical literature is more similar to PICKLE than computer science. Upon further exploration, we established that the inclusion of new types on which the models were not trained substantially impacts performance. The PICKLE corpus is, therefore, an important contribution to training resources for entity and RE in the plant sciences.

    

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