More Like this

1. Natural language processing systems for pathology parsing in limited data environments with uncertainty estimation

   https://doi.org/10.1093/jamiaopen/ooaa029  

   Odisho, Anobel Y ; Park, Briton ; Altieri, Nicholas ; DeNero, John ; Cooperberg, Matthew R ; Carroll, Peter R ; Yu, Bin ( October 2020 , JAMIA Open)

   null (Ed.)

   Abstract Objective Cancer is a leading cause of death, but much of the diagnostic information is stored as unstructured data in pathology reports. We aim to improve uncertainty estimates of machine learning-based pathology parsers and evaluate performance in low data settings. Materials and methods Our data comes from the Urologic Outcomes Database at UCSF which includes 3232 annotated prostate cancer pathology reports from 2001 to 2018. We approach 17 separate information extraction tasks, involving a wide range of pathologic features. To handle the diverse range of fields, we required 2 statistical models, a document classification method for pathologic features with a small set of possible values and a token extraction method for pathologic features with a large set of values. For each model, we used isotonic calibration to improve the model’s estimates of its likelihood of being correct. Results Our best document classifier method, a convolutional neural network, achieves a weighted F1 score of 0.97 averaged over 12 fields and our best extraction method achieves an accuracy of 0.93 averaged over 5 fields. The performance saturates as a function of dataset size with as few as 128 data points. Furthermore, while our document classifier methods have reliable uncertainty estimates, our extraction-based methods do not, but after isotonic calibration, expected calibration error drops to below 0.03 for all extraction fields. Conclusions We find that when applying machine learning to pathology parsing, large datasets may not always be needed, and that calibration methods can improve the reliability of uncertainty estimates. 

   more » « less
2. 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. 

   more » « less
3. Multi-Source Cross-Lingual Model Transfer: Learning What to Share

   Chen, Xilun ; Hassan Awadallah, Ahmed ; Hassan, Hany ; Wang, Wei ; Cardie, Claire ( January 2019 , Proceedings of the 57th Conference of the Association for Computational Linguistics (ACL))

   Modern NLP applications have enjoyed a great boost utilizing neural networks models. Such deep neural models, however, are not applicable to most human languages due to the lack of annotated training data for various NLP tasks. Cross-lingual transfer learning (CLTL) is a viable method for building NLP models for a low-resource target language by leveraging labeled data from other (source) languages. In this work, we focus on the multilingual transfer setting where training data in multiple source languages is leveraged to further boost target language performance. Unlike most existing methods that rely only on language-invariant features for CLTL, our approach coherently utilizes both language invariant and language-specific features at instance level. Our model leverages adversarial networks to learn language-invariant features, and mixture-of-experts models to dynamically exploit the similarity between the target language and each individual source language1. This enables our model to learn effectively what to share between various languages in the multilingual setup. Moreover, when coupled with unsupervised multilingual embeddings, our model can operate in a zero-resource setting where neither target language training data nor cross-lingual resources are available. Our model achieves significant performance gains over prior art, as shown in an extensive set of experiments over multiple text classification and sequence tagging. 

   more » « less
4. Active Heterogeneous Graph Neural Networks with Per-step Meta-Q-Learning

   https://doi.org/10.1109/ICDM54844.2022.00176  

   Zhang, Yuheng ; Xia, Yinglong ; Zhu, Yan ; Chi, Yuejie ; Ying, Lei ; Tong, Hanghang ( November 2022 , 2022 IEEE International Conference on Data Mining (ICDM))

   Recent years have witnessed the superior performance of heterogeneous graph neural networks (HGNNs) in dealing with heterogeneous information networks (HINs). Nonetheless, the success of HGNNs often depends on the availability of sufficient labeled training data, which can be very expensive to obtain in real scenarios. Active learning provides an effective solution to tackle the data scarcity challenge. For the vast majority of the existing work regarding active learning on graphs, they mainly focus on homogeneous graphs, and thus fall in short or even become inapplicable on HINs. In this paper, we study the active learning problem with HGNNs and propose a novel meta-reinforced active learning framework MetRA. Previous reinforced active learning algorithms train the policy network on labeled source graphs and directly transfer the policy to the target graph without any adaptation. To better exploit the information from the target graph in the adaptation phase, we propose a novel policy transfer algorithm based on meta-Q-learning termed per-step MQL. Empirical evaluations on HINs demonstrate the effectiveness of our proposed framework. The improvement over the best baseline is up to 7% in Micro-F1. 

   more » « less
5. DeepIsoFun: a deep domain adaptation approach to predict isoform functions

   https://doi.org/10.1093/bioinformatics/bty1017  

   Shaw, Dipan ; Chen, Hao ; Jiang, Tao ; Hancock, John ( December 2018 , Bioinformatics)

   Abstract Motivation Isoforms are mRNAs produced from the same gene locus by alternative splicing and may have different functions. Although gene functions have been studied extensively, little is known about the specific functions of isoforms. Recently, some computational approaches based on multiple instance learning have been proposed to predict isoform functions from annotated gene functions and expression data, but their performance is far from being desirable primarily due to the lack of labeled training data. To improve the performance on this problem, we propose a novel deep learning method, DeepIsoFun, that combines multiple instance learning with domain adaptation. The latter technique helps to transfer the knowledge of gene functions to the prediction of isoform functions and provides additional labeled training data. Our model is trained on a deep neural network architecture so that it can adapt to different expression distributions associated with different gene ontology terms. Results We evaluated the performance of DeepIsoFun on three expression datasets of human and mouse collected from SRA studies at different times. On each dataset, DeepIsoFun performed significantly better than the existing methods. In terms of area under the receiver operating characteristics curve, our method acquired at least 26% improvement and in terms of area under the precision-recall curve, it acquired at least 10% improvement over the state-of-the-art methods. In addition, we also study the divergence of the functions predicted by our method for isoforms from the same gene and the overall correlation between expression similarity and the similarity of predicted functions. Availability and implementation https://github.com/dls03/DeepIsoFun/ Supplementary information Supplementary data are available at Bioinformatics online. 

   more » « less