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Title: Bringing machine learning to research on intellectual and developmental disabilities: taking inspiration from neurological diseases

Intellectual and Developmental Disabilities (IDDs), such as Down syndrome, Fragile X syndrome, Rett syndrome, and autism spectrum disorder, usually manifest at birth or early childhood. IDDs are characterized by significant impairment in intellectual and adaptive functioning, and both genetic and environmental factors underpin IDD biology. Molecular and genetic stratification of IDDs remain challenging mainly due to overlapping factors and comorbidity. Advances in high throughput sequencing, imaging, and tools to record behavioral data at scale have greatly enhanced our understanding of the molecular, cellular, structural, and environmental basis of some IDDs. Fueled by the “big data” revolution, artificial intelligence (AI) and machine learning (ML) technologies have brought a whole new paradigm shift in computational biology. Evidently, the ML-driven approach to clinical diagnoses has the potential to augment classical methods that use symptoms and external observations, hoping to push the personalized treatment plan forward. Therefore, integrative analyses and applications of ML technology have a direct bearing on discoveries in IDDs. The application of ML to IDDs can potentially improve screening and early diagnosis, advance our understanding of the complexity of comorbidity, and accelerate the identification of biomarkers for clinical research and drug development. For more than five decades, the IDDRC network has supported a nexus of investigators at centers across the USA, all striving to understand the interplay between various factors underlying IDDs. In this review, we introduced fast-increasing multi-modal data types, highlighted example studies that employed ML technologies to illuminate factors and biological mechanisms underlying IDDs, as well as recent advances in ML technologies and their applications to IDDs and other neurological diseases. We discussed various molecular, clinical, and environmental data collection modes, including genetic, imaging, phenotypical, and behavioral data types, along with multiple repositories that store and share such data. Furthermore, we outlined some fundamental concepts of machine learning algorithms and presented our opinion on specific gaps that will need to be filled to accomplish, for example, reliable implementation of ML-based diagnosis technology in IDD clinics. We anticipate that this review will guide researchers to formulate AI and ML-based approaches to investigate IDDs and related conditions.

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Author(s) / Creator(s):
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Publisher / Repository:
Springer Science + Business Media
Date Published:
Journal Name:
Journal of Neurodevelopmental Disorders
Medium: X
Sponsoring Org:
National Science Foundation
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  1. 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. 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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. [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. [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. [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. [5] I. Caswell and B. Liang, “Recent Advances in Google Translate,” Google AI Blog: The latest from Google Research, 2020. [Online]. Available: [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. [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. [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. [9] A. P. Martinez, C. Cohen, K. Z. Hanley, and X. 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