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Novel machine learning approaches for improving structural discrimination in cryo-electron tomography

Award Number: R01GM134020
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/10/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Novel machine learning approaches for improving structural discrimination in cryo-electron tomography - Project Summary Cellular cryo-electron tomography (Cryo-ET) has made possible the observation of cellular organelles and macromolecular complexes at nanometer resolution with native conformations. The rapid increasing amount of Cryo-ET data available however brings along some major challenges for analysis which we will timely ad- dress in this proposal. We will design novel data-driven machine learning algorithms for improving structural discrimination and resolution. In particular, we have the following speciﬁc aims: (1) We will develop a novel Autoencoder and Iterative region Matching (AIM) algorithm for marker-free alignment of image tilt-series to re- construct tomograms with improved resolution; (2) We will develop a saliency-based auto-picking algorithm for better detecting macromolecular complexes, and combine it with an innovative 2D-to-3D framework to further improve structure detection accuracy; (3) We will design an end-to-end convolutional model for pose-invariant clustering of subtomograms. This model will produce an initial clustering which will be reﬁned by a new subto- mogram averaging algorithm that automatically down-weights subtomograms of noise and little contribution; (4) We will perform experimental evaluations by using previously reported bacterial secretion systems and mito- chondrial ultrastructures datasets to improve the ﬁnal resolution. Implementing algorithms in Aims 1-3, we will develop a user-friendly open-source graphical user interface -tom to directly beneﬁt the scientiﬁc community. -tom will be systematically compared with existing software including IMOD, EMAN2, and Relion on simulated and benchmark datasets. To facilitate distribution, -tom will be integrated into existing software platforms Sci- pion and TomoMiner. Our data-driven algorithms and software not only will facilitate and accelerate the future use of Cryo-ET, but also can be readily used on analyzing the existing large amounts of Cryo-ET data to im- prove our understanding of the structure, function, and spatial organization of macromolecular complexes in situ.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	4/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $326,671 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	4	6/22/2023	NON-COMPETING CONTINUATION	$326,671
														Subtotal = $326,671

Issue Date FY: 2022 ( Subtotal = $327,428 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	3	5/10/2022	NON-COMPETING CONTINUATION	$327,428
														Subtotal = $327,428

Issue Date FY: 2021 ( Subtotal = $440,887 )
2021	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	2	7/20/2021	NON-COMPETING CONTINUATION	$328,051
2021	2021	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	001	2	9/13/2021	SUPPLEMENT FOR EXPANSION	$112,836
														Subtotal = $440,887

Issue Date FY: 2020 ( Subtotal = $342,970 )
2020	2020	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	6/9/2020	NEW	$342,970
														Subtotal = $342,970

Grand Total All Awards = $1,437,956

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Novel machine learning approaches for improving structural discrimination in cryo-electron tomography

Award Number: R01GM134020

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/10/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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