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HMMER and Infernal: Finding distant homologs of sequences and RNA structures

Award Number: R01HG009116
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2016
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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HMMER and Infernal: Finding distant homologs of sequences and RNA structures - Project Summary/Abstract Genome sequence data is now available for hundreds of thousands of species. Our ability to exploit this vast trove of information about the molecular basis and evolution of life depends on sophisticated computational analysis tools. One important class of tools is proﬁle analysis software, for making consensus statistical models of multiple alignments of biological sequence families, and for using those models to sensitively detect homologs and make deep multiple alignments. Proﬁle analysis derives its power from the fact that despite the unbounded growth of sequence data, the majority of functional sequences can be condensed into a manageably small number of conserved families. Proﬁle software underlies numerous protein, RNA, and DNA sequence family databases. The systematic availability of deep multiple alignments (of many thousands of sequences) is enabling revolutionary advances in predicting molecular function and 3D structure by comparative sequence analysis. The HMMER and Infernal software packages from our laboratory are some of the most widely used tools for proﬁle analysis. HMMER implements proﬁle hidden Markov models (proﬁle HMMs) of primary sequence consensus, typically for protein domains and conserved DNA elements. Infernal implements proﬁle stochastic context-free grammars (proﬁle SCFGs) of RNA secondary structure and sequence consensus. In the context of the continued development of these packages, this proposal has three speciﬁc aims for new lines of research that we expect to lead to major improvements in the accuracy, utility, and computational efﬁciency of proﬁle anal- ysis. The ﬁrst aim proposes to develop a discontinuous Markov model of nonhomologous sequences, to improve the ability to distinguish homologs from nonhomologs and reduce the false positive rate of database searches. The second aim proposes to develop sketching methods for efﬁciently representing the voluminous results of a database homology search with a subset of the most phylogenetically informative hits. The third aim proposes to develop adaptive computation methods to ﬂexibly harness the complex mix of CPU/GPU processors, mem- ory, and storage in modern hardware architectures, enabling efﬁcient scalable computation and near-interactive database search times.


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 = $522,781 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	9	9/4/2025	NON-COMPETING CONTINUATION	$522,781
														Subtotal = $522,781

Issue Date FY: 2024 ( Subtotal = $522,781 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	8	7/26/2024	NON-COMPETING CONTINUATION	$522,781
														Subtotal = $522,781

Issue Date FY: 2023 ( Subtotal = $533,450 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	7	6/21/2023	NON-COMPETING CONTINUATION	$533,450
														Subtotal = $533,450

Issue Date FY: 2022 ( Subtotal = $533,450 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	002	6	8/12/2022	NON-COMPETING CONTINUATION	$533,450
2022	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	001	5	11/16/2021	COMPETING CONTINUATION	$187,327
2022	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	4	11/16/2021	NON-COMPETING CONTINUATION	-$187,327
														Subtotal = $533,450

Issue Date FY: 2021 ( Subtotal = $533,450 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	5	9/10/2021	COMPETING CONTINUATION	$533,450
														Subtotal = $533,450

Issue Date FY: 2019 ( Subtotal = $422,500 )
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	4	6/24/2019	NON-COMPETING CONTINUATION	$422,500
														Subtotal = $422,500

Issue Date FY: 2018 ( Subtotal = $422,500 )
2018	2018	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	3	7/2/2018	NON-COMPETING CONTINUATION	$422,500
														Subtotal = $422,500

Issue Date FY: 2017 ( Subtotal = $422,500 )
2017	2017	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	2	7/8/2017	NON-COMPETING CONTINUATION	$422,500
														Subtotal = $422,500

Issue Date FY: 2016 ( Subtotal = $422,500 )
2016	2016	HARVARD UNIVERSITY PRESIDENT & FELLOWS	HOLYOKE 466, 1350 MASS AVENUE	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Human Genome Research	000	1	9/16/2016	NEW	$422,500
														Subtotal = $422,500

Grand Total All Awards = $4,335,912

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HMMER and Infernal: Finding distant homologs of sequences and RNA structures

Award Number: R01HG009116

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/16/2016

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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