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1. A Theory of Selective Prediction

   Qiao, Mingda ; Valiant, Gregory ( January 2019 , Conference on Learning Theory (COLT))

   We consider a model of selective prediction, where the prediction algorithm is given a data sequence in an online fashion and asked to predict a pre-specified statistic of the upcoming data points. The algorithm is allowed to choose when to make the prediction as well as the length of the prediction window, possibly depending on the observations so far. We prove that, even without any distributional assumption on the input data stream, a large family of statistics can be estimated to non-trivial accuracy. To give one concrete example, suppose that we are given access to an arbitrary binary sequence x1, . . . , xn of length n. Our goal is to accurately predict the average observation, and we are allowed to choose the window over which the prediction is made: for some t < n and m < n − t, after seeing t observations we predict the average of x_{t+1},..., x{t+m}. This particular problem was first studied in [Dru13] and referred to as the “density prediction game”. We show that the expected squared error of our prediction can be bounded by O(1/log n) and prove a matching lower bound, which resolves an open question raised in [Dru13]. Thismore »result holds for any sequence (that is not adaptive to when the prediction is made, or the predicted value), and the expectation of the error is with respect to the randomness of the prediction algorithm. Our results apply to more general statistics of a sequence of observations, and we highlight several open directions for future work.« 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 notmore »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.« less
3. Efficient Algorithms for Least Square Piecewise Polynomial Regression

   Lokshtanov, Daniel ; Suri, Subhash ; Xue, Jie ( September 2021 , ESA21: Proceedings of European Symposium on Algorithms)

   We present approximation and exact algorithms for piecewise regression of univariate and bivariate data using fixed-degree polynomials. Specifically, given a set S of n data points (x1, y1), . . . , (xn, yn) ∈ Rd × R where d ∈ {1, 2}, the goal is to segment xi’s into some (arbitrary) number of disjoint pieces P1, . . . , Pk, where each piece Pj is associated with a fixed-degree polynomial fj : Rd → R, to minimize the total loss function λk+􏰄ni=1(yi −f(xi))2, where λ ≥ 0 is a regularization term that penalizes model complexity (number of pieces) and f : 􏰇kj=1 Pj → R is the piecewise polynomial function defined as f|Pj = fj. The pieces P1,...,Pk are disjoint intervals of R in the case of univariate data and disjoint axis-aligned rectangles in the case of bivariate data. Our error approximation allows use of any fixed-degree polynomial, not just linear functions. Our main results are the following. For univariate data, we present a (1 + ε)-approximation algorithm with time complexity O(nε log1ε), assuming that data is presented in sorted order of xi’s. For bivariate data, we √ present three results: a sub-exponential exact algorithm with running timemore »nO( n); a polynomial-time constant- approximation algorithm; and a quasi-polynomial time approximation scheme (QPTAS). The bivariate case is believed to be NP-hard in the folklore but we could not find a published record in the literature, so in this paper we also present a hardness proof for completeness.« less
4. Estimating location parameters in sample-heterogeneous distributions

   https://doi.org/10.1093/imaiai/iaab013  

   Pensia, Ankit ; Jog, Varun ; Loh, Po-Ling ( June 2021 , Information and Inference: A Journal of the IMA)

   Abstract Estimating the mean of a probability distribution using i.i.d. samples is a classical problem in statistics, wherein finite-sample optimal estimators are sought under various distributional assumptions. In this paper, we consider the problem of mean estimation when independent samples are drawn from $d$-dimensional non-identical distributions possessing a common mean. When the distributions are radially symmetric and unimodal, we propose a novel estimator, which is a hybrid of the modal interval, shorth and median estimators and whose performance adapts to the level of heterogeneity in the data. We show that our estimator is near optimal when data are i.i.d. and when the fraction of ‘low-noise’ distributions is as small as $\varOmega \left (\frac{d \log n}{n}\right )$, where $n$ is the number of samples. We also derive minimax lower bounds on the expected error of any estimator that is agnostic to the scales of individual data points. Finally, we extend our theory to linear regression. In both the mean estimation and regression settings, we present computationally feasible versions of our estimators that run in time polynomial in the number of data points.
5. Prediction and Outlier Detection in Classification Problems

   https://doi.org/10.1111/rssb.12443  

   Guan, Leying ; Tibshirani, Robert ( February 2022 , Journal of the Royal Statistical Society Series B: Statistical Methodology)

   We consider the multi-class classification problem when the training data and the out-of-sample test data may have different distributions and propose a method called BCOPS (balanced and conformal optimized prediction sets). BCOPS constructs a prediction set C(x) as a subset of class labels, possibly empty. It tries to optimize the out-of-sample performance, aiming to include the correct class and to detect outliers x as often as possible. BCOPS returns no prediction (corresponding to C(x) equal to the empty set) if it infers x to be an outlier. The proposed method combines supervised learning algorithms with conformal prediction to minimize a misclassification loss averaged over the out-of-sample distribution. The constructed prediction sets have a finite sample coverage guarantee without distributional assumptions. We also propose a method to estimate the outlier detection rate of a given procedure. We prove asymptotic consistency and optimality of our proposals under suitable assumptions and illustrate our methods on real data examples.