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1. Workforce Capacity Development and the Digital Extended Specimen

   https://doi.org/10.3897/biss.5.73927  

   Monfils, Anna ; Ellwood, Elizabeth R. ( September 2021 , Biodiversity Information Science and Standards)

   As we look to the future of natural history collections and a global integration of biodiversity data, we are reliant on a diverse workforce with the skills necessary to build, grow, and support the data, tools, and resources of the Digital Extended Specimen (DES; Webster 2019, Lendemer et al. 2020, Hardisty 2020). Future “DES Data Curators” – those who will be charged with maintaining resources created through the DES – will require skills and resources beyond what is currently available to most natural history collections staff. In training the workforce to support the DES we have an opportunity to broaden our community and ensure that, through the expansion of biodiversity data, the workforce landscape itself is diverse, equitable, inclusive, and accessible. A fully-implemented DES will provide training that encapsulates capacity building, skills development, unifying protocols and best practices guidance, and cutting-edge technology that also creates inclusive, equitable, and accessible systems, workflows, and communities. As members of the biodiversity community and the current workforce, we can leverage our knowledge and skills to develop innovative training models that: include a range of educational settings and modalities; address the needs of new communities not currently engaged with digital data; from their onset, provide attribution for past and future work and do not perpetuate the legacy of colonial practices and historic inequalities found in many physical natural history collections. Recent reports from the Biodiversity Collections Network (BCoN 2019) and the National Academies of Science, Engineering and Medicine (National Academies of Sciences, Engineering, and Medicine 2020) specifically address workforce needs in support of the DES. To address workforce training and inclusivity within the context of global data integration, the Alliance for Biodiversity Knowledge included a topic on Workforce capacity development and inclusivity in Phase 2 of the consultation on Converging Digital Specimens and Extended Specimens - Towards a global specification for data integration. Across these efforts, several common themes have emerged relative to workforce training and the DES. A call for a community needs assessment: As a community, we have several unknowns related to the current collections workforce and training needs. We would benefit from a baseline assessment of collections professionals to define current job responsibilities, demographics, education and training, incentives, compensation, and benefits. This includes an evaluation of current employment prospects and opportunities. Defined skills and training for the 21st century collections professional: We need to be proactive and define the 21st century workforce skills necessary to support the development and implementation of the DES. When we define the skills and content needs we can create appropriate training opportunities that include scalable materials for capacity building, educational materials that develop relevant skills, unifying protocols across the DES network, and best practices guidance for professionals. Training for data end-users: We need to train data end-users in biodiversity and data science at all levels of formal and informal education from primary and secondary education through the existing workforce. This includes developing training and educational materials, creating data portals, and building analyses that are inclusive, accessible, and engage the appropriate community of science educators, data scientists, and biodiversity researchers. Foster a diverse, equitable, inclusive, and accessible and professional workforce: As the DES develops and new tools and resources emerge, we need to be intentional in our commitment to building tools that are accessible and in assuring that access is equitable. This includes establishing best practices to ensure the community providing and accessing data is inclusive and representative of the diverse global community of potential data providers and users. Upfront, we must acknowledge and address issues of historic inequalities and colonial practices and provide appropriate attribution for past and future work while ensuring legal and regulatory compliance. Efforts must include creating transparent linkages among data and the humans that create the data that drives the DES. In this presentation, we will highlight recommendations for building workforce capacity within the DES that are diverse, inclusive, equitable and accessible, take into account the requirements of the biodiversity science community, and that are flexible to meet the needs of an evolving field. 

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2. Highlights and Outcomes of the 2021 Global Community Consultation

   https://doi.org/10.3897/biss.5.72716  

   Ellwood, Elizabeth R. ; Bentley, Andrew ; Buschbom, Jutta ; Hardisty, Alex ; Mast, Austin ; Miller, Joe ; Monfils, Anna ; Nelson, Gil ; Paul, Deborah L ( August 2021 , Biodiversity Information Science and Standards)

   International collaboration between collections, aggregators, and researchers within the biodiversity community and beyond is becoming increasingly important in our efforts to support biodiversity, conservation and the life of the planet. The social, technical, logistical and financial aspects of an equitable biodiversity data landscape – from workforce training and mobilization of linked specimen data, to data integration, use and publication – must be considered globally and within the context of a growing biodiversity crisis. In recent years, several initiatives have outlined paths forward that describe how digital versions of natural history specimens can be extended and linked with associated data. In the United States, Webster (2017) presented the “extended specimen”, which was expanded upon by Lendemer et al. (2019) through the work of the Biodiversity Collections Network (BCoN). At the same time, a “digital specimen” concept was developed by DiSSCo in Europe (Hardisty 2020). Both the extended and digital specimen concepts depict a digital proxy of an analog natural history specimen, whose digital nature provides greater capabilities such as being machine-processable, linkages with associated data, globally accessible information-rich biodiversity data, improved tracking, attribution and annotation, additional opportunities for data use and cross-disciplinary collaborations forming the basis for FAIR (Findable, Accessible, Interoperable, Reproducible) and equitable sharing of benefits worldwide, and innumerable other advantages, with slight variation in how an extended or digital specimen model would be executed. Recognizing the need to align the two closely-related concepts, and to provide a place for open discussion around various topics of the Digital Extended Specimen (DES; the current working name for the joined concepts), we initiated a virtual consultation on the discourse platform hosted by the Alliance for Biodiversity Knowledge through GBIF. This platform provided a forum for threaded discussions around topics related and relevant to the DES. The goals of the consultation align with the goals of the Alliance for Biodiversity Knowledge: expand participation in the process, build support for further collaboration, identify use cases, identify significant challenges and obstacles, and develop a comprehensive roadmap towards achieving the vision for a global specification for data integration. In early 2021, Phase 1 launched with five topics: Making FAIR data for specimens accessible; Extending, enriching and integrating data; Annotating specimens and other data; Data attribution; and Analyzing/mining specimen data for novel applications. This round of full discussion was productive and engaged dozens of contributors, with hundreds of posts and thousands of views. During Phase 1, several deeper, more technical, or additional topics of relevance were identified and formed the foundation for Phase 2 which began in May 2021 with the following topics: Robust access points and data infrastructure alignment; Persistent identifier (PID) scheme(s); Meeting legal/regulatory, ethical and sensitive data obligations; Workforce capacity development and inclusivity; Transactional mechanisms and provenance; and Partnerships to collaborate more effectively. In Phase 2 fruitful progress was made towards solutions to some of these complex functional and technical long-term goals. Simultaneously, our commitment to open participation was reinforced, through increased efforts to involve new voices from allied and complementary fields. Among a wealth of ideas expressed, the community highlighted the need for unambiguous persistent identifiers and a dedicated agent to assign them, support for a fully linked system that includes robust publishing mechanisms, strong support for social structures that build trustworthiness of the system, appropriate attribution of legacy and new work, a system that is inclusive, removed from colonial practices, and supportive of creative use of biodiversity data, building a truly global data infrastructure, balancing open access with legal obligations and ethical responsibilities, and the partnerships necessary for success. These two consultation periods, and the myriad activities surrounding the online discussion, produced a wide variety of perspectives, strategies, and approaches to converging the digital and extended specimen concepts, and progressing plans for the DES -- steps necessary to improve access to research-ready data to advance our understanding of the diversity and distribution of life. Discussions continue and we hope to include your contributions to the DES in future implementation plans. 

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3. Expanding an HPC Cluster to Support the Computational Demands of Digital Pathology

   https://doi.org/10.1109/SPMB.2018.8615614  

   Campbell, C. ; Mecca, N. ; Duong, T. ; Obeid, I. ; Picone, J. ( December 2018 , IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   Obeid, Iyad ; Selesnick, Ivan ; Picone, Joseph (Ed.)

   The goal of this work was to design a low-cost computing facility that can support the development of an open source digital pathology corpus containing 1M images [1]. A single image from a clinical-grade digital pathology scanner can range in size from hundreds of megabytes to five gigabytes. A 1M image database requires over a petabyte (PB) of disk space. To do meaningful work in this problem space requires a significant allocation of computing resources. The improvements and expansions to our HPC (highperformance computing) cluster, known as Neuronix [2], required to support working with digital pathology fall into two broad categories: computation and storage. To handle the increased computational burden and increase job throughput, we are using Slurm [3] as our scheduler and resource manager. For storage, we have designed and implemented a multi-layer filesystem architecture to distribute a filesystem across multiple machines. These enhancements, which are entirely based on open source software, have extended the capabilities of our cluster and increased its cost-effectiveness. Slurm has numerous features that allow it to generalize to a number of different scenarios. Among the most notable is its support for GPU (graphics processing unit) scheduling. GPUs can offer a tremendous performance increase in machine learning applications [4] and Slurm’s built-in mechanisms for handling them was a key factor in making this choice. Slurm has a general resource (GRES) mechanism that can be used to configure and enable support for resources beyond the ones provided by the traditional HPC scheduler (e.g. memory, wall-clock time), and GPUs are among the GRES types that can be supported by Slurm [5]. In addition to being able to track resources, Slurm does strict enforcement of resource allocation. This becomes very important as the computational demands of the jobs increase, so that they have all the resources they need, and that they don’t take resources from other jobs. It is a common practice among GPU-enabled frameworks to query the CUDA runtime library/drivers and iterate over the list of GPUs, attempting to establish a context on all of them. Slurm is able to affect the hardware discovery process of these jobs, which enables a number of these jobs to run alongside each other, even if the GPUs are in exclusive-process mode. To store large quantities of digital pathology slides, we developed a robust, extensible distributed storage solution. We utilized a number of open source tools to create a single filesystem, which can be mounted by any machine on the network. At the lowest layer of abstraction are the hard drives, which were split into 4 60-disk chassis, using 8TB drives. To support these disks, we have two server units, each equipped with Intel Xeon CPUs and 128GB of RAM. At the filesystem level, we have implemented a multi-layer solution that: (1) connects the disks together into a single filesystem/mountpoint using the ZFS (Zettabyte File System) [6], and (2) connects filesystems on multiple machines together to form a single mountpoint using Gluster [7]. ZFS, initially developed by Sun Microsystems, provides disk-level awareness and a filesystem which takes advantage of that awareness to provide fault tolerance. At the filesystem level, ZFS protects against data corruption and the infamous RAID write-hole bug by implementing a journaling scheme (the ZFS intent log, or ZIL) and copy-on-write functionality. Each machine (1 controller + 2 disk chassis) has its own separate ZFS filesystem. Gluster, essentially a meta-filesystem, takes each of these, and provides the means to connect them together over the network and using distributed (similar to RAID 0 but without striping individual files), and mirrored (similar to RAID 1) configurations [8]. By implementing these improvements, it has been possible to expand the storage and computational power of the Neuronix cluster arbitrarily to support the most computationally-intensive endeavors by scaling horizontally. We have greatly improved the scalability of the cluster while maintaining its excellent price/performance ratio [1]. 

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4. Candidate Periodically Variable Quasars from the Dark Energy Survey and the Sloan Digital Sky Survey

   https://doi.org/10.1093/mnras/staa2957  

   Chen, Yu-Ching ; Liu, Xin ; Liao, Wei-Ting ; Holgado, A Miguel ; Guo, Hengxiao ; Gruendl, Robert A ; Morganson, Eric ; Shen, Yue ; Zhang, Kaiwen ; Abbott, Tim M ; et al ( December 2020 , Monthly Notices of the Royal Astronomical Society)

   null (Ed.)

   Abstract Periodically variable quasars have been suggested as close binary supermassive black holes. We present a systematic search for periodic light curves in 625 spectroscopically confirmed quasars with a median redshift of 1.8 in a 4.6 deg2 overlapping region of the Dark Energy Survey Supernova (DES-SN) fields and the Sloan Digital Sky Survey Stripe 82 (SDSS-S82). Our sample has a unique 20-year long multi-color (griz) light curve enabled by combining DES-SN Y6 observations with archival SDSS-S82 data. The deep imaging allows us to search for periodic light curves in less luminous quasars (down to r ∼23.5 mag) powered by less massive black holes (with masses ≳ 108.5M⊙) at high redshift for the first time. We find five candidates with significant (at >99.74% single-frequency significance in at least two bands with a global p-value of ∼7 × 10−4–3× 10−3 accounting for the look-elsewhere effect) periodicity with observed periods of ∼3–5 years (i.e., 1–2 years in rest frame) having ∼4–6 cycles spanned by the observations. If all five candidates are periodically variable quasars, this translates into a detection rate of ${\sim }0.8^{+0.5}_{-0.3}$% or ${\sim }1.1^{+0.7}_{-0.5}$ quasar per deg2. Our detection rate is 4–80 times larger than those found by previous searches using shallower surveys over larger areas. This discrepancy is likely caused by differences in the quasar populations probed and the survey data qualities. We discuss implications on the future direct detection of low-frequency gravitational waves. Continued photometric monitoring will further assess the robustness and characteristics of these candidate periodic quasars to determine their physical origins. 

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5. 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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