Detecting Very Weak Signals: A Mixed Strategy to Deal with Biologically Relevant Information

In many biological investigations, the relevant information does not coincide with the most powerful signals (most elevated eigenvalues, dominant frequencies, most populated clusters...), but very often hides in minor features that are difficult to discriminate from random noise. Here we propose an...

Full description

Saved in:
Bibliographic Details
Published inAlgorithms Vol. 18; no. 9; p. 581
Main Authors Vici, Alessandro, Zeuner, Ann, Giuliani, Alessandro
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 13.09.2025
Subjects
Online AccessGet full text
ISSN1999-4893
1999-4893
DOI10.3390/a18090581

Cover

Abstract In many biological investigations, the relevant information does not coincide with the most powerful signals (most elevated eigenvalues, dominant frequencies, most populated clusters...), but very often hides in minor features that are difficult to discriminate from random noise. Here we propose an algorithm that, by the combined use of a non-linear cluster analysis procedure and a strategy to discriminate minor signal components from noise, allows singling out biologically relevant hidden information. We tested the algorithm on a sparse data set corresponding to single-cell RNA-Seq measures, being able to identify a very small population of cells in charge of the immune response toward cancer tissue.
AbstractList In many biological investigations, the relevant information does not coincide with the most powerful signals (most elevated eigenvalues, dominant frequencies, most populated clusters...), but very often hides in minor features that are difficult to discriminate from random noise. Here we propose an algorithm that, by the combined use of a non-linear cluster analysis procedure and a strategy to discriminate minor signal components from noise, allows singling out biologically relevant hidden information. We tested the algorithm on a sparse data set corresponding to single-cell RNA-Seq measures, being able to identify a very small population of cells in charge of the immune response toward cancer tissue.
Author Giuliani, Alessandro
Zeuner, Ann
Vici, Alessandro
Author_xml – sequence: 1
  givenname: Alessandro
  orcidid: 0009-0001-1701-1270
  surname: Vici
  fullname: Vici, Alessandro
– sequence: 2
  givenname: Ann
  orcidid: 0000-0002-8295-3715
  surname: Zeuner
  fullname: Zeuner, Ann
– sequence: 3
  givenname: Alessandro
  orcidid: 0000-0002-4640-804X
  surname: Giuliani
  fullname: Giuliani, Alessandro
BookMark eNpNkEtLAzEYRYNUsK0u_AcBVy5G85jJJO5q66NQEWzRjTCk6ZcxdTqpmVSdf29LRVzdu7gcuKeHOrWvAaFTSi44V-RSU0kUySQ9QF2qlEpSqXjnXz9CvaZZEiIyJWgXvY4ggomuLvEzhBa_gH7HU1fWumqu8AA_uG9Y4GkMOkLZ4ujxCHSFv1x8w9fOV750RldVi5-ggk9dRzyurQ8rHZ2vj9Gh3XLg5Df7aHZ7MxveJ5PHu_FwMEmMymmScwVcUKKslvO5EDoTuU2BSZUTkhvGCMm4NJSwTHHQEjIjuZ5Ta6lZ5MzyPjrbY9fBf2ygicXSb8LuQcFZlqaCsZRvV-f7lQm-aQLYYh3cSoe2oKTYuSv-3PEfO11hbg
Cites_doi 10.1016/j.gpb.2020.07.004
10.3389/fgene.2022.828479
10.1186/1471-2105-7-194
10.20944/preprints202502.0391.v1
10.1101/066498
10.1038/s41590-022-01197-z
10.3390/stats7010004
10.3389/fbinf.2025.1519468
10.1002/wcms.1099
10.1038/nrg2825
10.1145/1015330.1015408
10.3390/diagnostics11061071
10.3934/math.20241222
10.1038/s41467-025-56347-2
10.1038/75556
10.1038/nbt.4314
10.1016/S0014-5793(01)02973-8
ContentType Journal Article
Copyright 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
DBID AAYXX
CITATION
3V.
7SC
7TB
7XB
8AL
8FD
8FE
8FG
8FK
ABJCF
ABUWG
AFKRA
ARAPS
AZQEC
BENPR
BGLVJ
CCPQU
DWQXO
FR3
GNUQQ
HCIFZ
JQ2
K7-
KR7
L6V
L7M
L~C
L~D
M0N
M7S
P62
PHGZM
PHGZT
PIMPY
PKEHL
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
PTHSS
Q9U
DOI 10.3390/a18090581
DatabaseName CrossRef
ProQuest Central (Corporate)
Computer and Information Systems Abstracts
Mechanical & Transportation Engineering Abstracts
ProQuest Central (purchase pre-March 2016)
Computing Database (Alumni Edition)
Technology Research Database
ProQuest SciTech Collection
ProQuest Technology Collection
ProQuest Central (Alumni) (purchase pre-March 2016)
Materials Science & Engineering Collection
ProQuest Central (Alumni)
ProQuest Central UK/Ireland
Advanced Technologies & Aerospace Collection
ProQuest Central Essentials
ProQuest Central
Technology Collection
ProQuest One Community College
ProQuest Central
Engineering Research Database
ProQuest Central Student
SciTech Premium Collection
ProQuest Computer Science Collection
Computer Science Database
Civil Engineering Abstracts
ProQuest Engineering Collection
Advanced Technologies Database with Aerospace
Computer and Information Systems Abstracts – Academic
Computer and Information Systems Abstracts Professional
Computing Database
Engineering Database
ProQuest Advanced Technologies & Aerospace Collection
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest One Academic Middle East (New)
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
Engineering Collection
ProQuest Central Basic
DatabaseTitle CrossRef
Publicly Available Content Database
Computer Science Database
ProQuest Central Student
Technology Collection
Technology Research Database
Computer and Information Systems Abstracts – Academic
ProQuest One Academic Middle East (New)
Mechanical & Transportation Engineering Abstracts
ProQuest Advanced Technologies & Aerospace Collection
ProQuest Central Essentials
ProQuest Computer Science Collection
Computer and Information Systems Abstracts
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest Central China
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest Engineering Collection
ProQuest Central Korea
ProQuest Central (New)
Advanced Technologies Database with Aerospace
Engineering Collection
Advanced Technologies & Aerospace Collection
Civil Engineering Abstracts
ProQuest Computing
Engineering Database
ProQuest Central Basic
ProQuest Computing (Alumni Edition)
ProQuest One Academic Eastern Edition
ProQuest Technology Collection
ProQuest SciTech Collection
Computer and Information Systems Abstracts Professional
ProQuest One Academic UKI Edition
Materials Science & Engineering Collection
Engineering Research Database
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
DatabaseTitleList CrossRef
Publicly Available Content Database
Database_xml – sequence: 1
  dbid: 8FG
  name: ProQuest Technology Collection
  url: https://search.proquest.com/technologycollection1
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Computer Science
EISSN 1999-4893
ExternalDocumentID 10_3390_a18090581
GroupedDBID 23M
2WC
5VS
8FE
8FG
AADQD
AAFWJ
AAYXX
ABDBF
ABJCF
ABUWG
ACUHS
ADBBV
AFKRA
AFPKN
AFZYC
ALMA_UNASSIGNED_HOLDINGS
AMVHM
ARAPS
AZQEC
BCNDV
BENPR
BGLVJ
BPHCQ
CCPQU
CITATION
DWQXO
E3Z
ESX
GNUQQ
GROUPED_DOAJ
HCIFZ
IAO
ICD
ITC
J9A
K6V
K7-
KQ8
L6V
M7S
MODMG
M~E
OK1
OVT
P2P
PHGZM
PHGZT
PIMPY
PQGLB
PQQKQ
PROAC
PTHSS
PUEGO
TR2
TUS
3V.
7SC
7TB
7XB
8AL
8FD
8FK
FR3
JQ2
KR7
L7M
L~C
L~D
M0N
P62
PKEHL
PQEST
PQUKI
PRINS
Q9U
ID FETCH-LOGICAL-c971-739e36109fa8bb66a567f4e2897007c2200538c102593ea8e5c83ab1ff1cd72f3
IEDL.DBID 8FG
ISSN 1999-4893
IngestDate Fri Sep 26 22:09:10 EDT 2025
Thu Sep 18 00:22:23 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 9
Language English
License https://creativecommons.org/licenses/by/4.0
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c971-739e36109fa8bb66a567f4e2897007c2200538c102593ea8e5c83ab1ff1cd72f3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ORCID 0000-0002-8295-3715
0009-0001-1701-1270
0000-0002-4640-804X
OpenAccessLink https://www.proquest.com/docview/3254462243?pq-origsite=%requestingapplication%
PQID 3254462243
PQPubID 2032439
ParticipantIDs proquest_journals_3254462243
crossref_primary_10_3390_a18090581
PublicationCentury 2000
PublicationDate 2025-09-13
PublicationDateYYYYMMDD 2025-09-13
PublicationDate_xml – month: 09
  year: 2025
  text: 2025-09-13
  day: 13
PublicationDecade 2020
PublicationPlace Basel
PublicationPlace_xml – name: Basel
PublicationTitle Algorithms
PublicationYear 2025
Publisher MDPI AG
Publisher_xml – name: MDPI AG
References Leek (ref_4) 2010; 11
Ashburner (ref_18) 2000; 25
ref_14
Zemmour (ref_16) 2022; 23
ref_13
Becht (ref_17) 2019; 37
Khan (ref_11) 2024; 9
ref_10
Giuliani (ref_1) 2024; 7
ref_3
Mondal (ref_12) 2025; 16
Francescangeli (ref_19) 2023; 42
ref_8
Crescenzi (ref_9) 2001; 507
Jolicoeur (ref_2) 1960; 24
ref_7
Huang (ref_15) 2021; 19
Daidone (ref_5) 2012; 2
ref_6
References_xml – volume: 19
  start-page: 267
  year: 2021
  ident: ref_15
  article-title: Evaluation of cell type annotation R packages on single-cell RNA-seq data
  publication-title: Genom. Proteom. Bioinform.
  doi: 10.1016/j.gpb.2020.07.004
– ident: ref_14
  doi: 10.3389/fgene.2022.828479
– ident: ref_7
  doi: 10.1186/1471-2105-7-194
– ident: ref_10
  doi: 10.20944/preprints202502.0391.v1
– volume: 42
  start-page: 197
  year: 2023
  ident: ref_19
  article-title: Dormancy, stemness, and therapy resistance: Interconnected players in cancer evolution
  publication-title: Cancer Metastasis Rev.
– ident: ref_3
  doi: 10.1101/066498
– volume: 23
  start-page: 643
  year: 2022
  ident: ref_16
  article-title: The ImmGen consortium OpenSource T cell project
  publication-title: Nat. Immunol.
  doi: 10.1038/s41590-022-01197-z
– volume: 7
  start-page: 54
  year: 2024
  ident: ref_1
  article-title: On the (Apparently) Paradoxical Role of Noise in the Recognition of Signal Character of Minor Principal Components
  publication-title: Stats
  doi: 10.3390/stats7010004
– ident: ref_13
  doi: 10.3389/fbinf.2025.1519468
– volume: 2
  start-page: 762
  year: 2012
  ident: ref_5
  article-title: Essential dynamics: Foundation and applications
  publication-title: WIREs Comput. Mol. Sci.
  doi: 10.1002/wcms.1099
– volume: 11
  start-page: 733
  year: 2010
  ident: ref_4
  article-title: Tackling the widespread and critical impact of batch effects in high-throughput data
  publication-title: Nat. Rev. Genet.
  doi: 10.1038/nrg2825
– ident: ref_8
  doi: 10.1145/1015330.1015408
– volume: 24
  start-page: 339
  year: 1960
  ident: ref_2
  article-title: Size and shape variation in the painted turtle. A principal component analysis
  publication-title: Growth
– ident: ref_6
  doi: 10.3390/diagnostics11061071
– volume: 9
  start-page: 25070
  year: 2024
  ident: ref_11
  article-title: Addressing limitations of the K-means clustering algorithm: Outliers, non-spherical data, and optimal cluster selection
  publication-title: MATH
  doi: 10.3934/math.20241222
– volume: 16
  start-page: 1378
  year: 2025
  ident: ref_12
  article-title: Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche
  publication-title: Nat. Commun.
  doi: 10.1038/s41467-025-56347-2
– volume: 25
  start-page: 25
  year: 2000
  ident: ref_18
  article-title: Gene Ontology: Tool for the unification of biology
  publication-title: Nat. Genet.
  doi: 10.1038/75556
– volume: 37
  start-page: 38
  year: 2019
  ident: ref_17
  article-title: Dimensionality reduction for visualizing single-cell data using UMAP
  publication-title: Nat. Biotechnol.
  doi: 10.1038/nbt.4314
– volume: 507
  start-page: 114
  year: 2001
  ident: ref_9
  article-title: The main biological determinants of tumor line taxonomy elucidated by a principal component analysis of microarray data
  publication-title: FEBS Lett.
  doi: 10.1016/S0014-5793(01)02973-8
SSID ssj0065961
Score 2.3526337
Snippet In many biological investigations, the relevant information does not coincide with the most powerful signals (most elevated eigenvalues, dominant frequencies,...
SourceID proquest
crossref
SourceType Aggregation Database
Index Database
StartPage 581
SubjectTerms Algorithms
Cluster analysis
Clustering
Data analysis
Datasets
Eigenvalues
Gene expression
Random noise
Title Detecting Very Weak Signals: A Mixed Strategy to Deal with Biologically Relevant Information
URI https://www.proquest.com/docview/3254462243
Volume 18
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAFT
  databaseName: Open Access Digital Library
  customDbUrl:
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: KQ8
  dateStart: 20080101
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVAON
  databaseName: DOAJ: Directory of Open Access Journals
  customDbUrl:
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: DOA
  dateStart: 20080101
  isFulltext: true
  titleUrlDefault: https://www.doaj.org/
  providerName: Directory of Open Access Journals
– providerCode: PRVEBS
  databaseName: EBSCOhost Academic Search Ultimate
  customDbUrl: https://search.ebscohost.com/login.aspx?authtype=ip,shib&custid=s3936755&profile=ehost&defaultdb=asn
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: ABDBF
  dateStart: 20091201
  isFulltext: true
  titleUrlDefault: https://search.ebscohost.com/direct.asp?db=asn
  providerName: EBSCOhost
– providerCode: PRVHPJ
  databaseName: ROAD: Directory of Open Access Scholarly Resources
  customDbUrl:
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: M~E
  dateStart: 20080101
  isFulltext: true
  titleUrlDefault: https://road.issn.org
  providerName: ISSN International Centre
– providerCode: PRVPQU
  databaseName: ProQuest Databases
  customDbUrl: http://www.proquest.com/pqcentral?accountid=15518
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: BENPR
  dateStart: 20080301
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Technology Collection
  customDbUrl:
  eissn: 1999-4893
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0065961
  issn: 1999-4893
  databaseCode: 8FG
  dateStart: 20080301
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/technologycollection1
  providerName: ProQuest
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1NTwIxEG0ULl78NqJIGuN1A9tuu8WLQQGJicQgKgeTTdttDdEAAiby7-3sdjVcPG96menMm5nuvIfQBZdUSSt0YBoumtylEIFKLQsE5cwQkiqmM7bPPu89RXcjNvIDt4X_rbLIiVmiTqcaZuR1Clxa3AEOvZp9BqAaBa-rXkJjE5VD4m4SbIp3b4tMzFmThzmbEHWtfV0CV1WDiXAdg9ZTcIYr3V207QtC3Mo9uIc2zGQf7RRiC9jH3gF6bRuY9zukwc9mvsIvRr7jx_Eb8B9f4ha-H3-bFHuy2RVeTnHb1YAY5qw4F5wEd3ys8AA2yp09sd9EAs8comG3M7zpBV4aIdDNOAxi2jQUiNKtFEpxLhmPbWRc8xQ7zNcERkVUaFc8sCY1UhimBZUqtDbUaUwsPUKlyXRijhEmKaGRpTbS8GCauoY4likhRkh3LNKqgs4LWyWznAAjcY0DGDT5NWgFVQsrJj4GFsmfx07-_3yKtgio6oIwA62i0nL-Zc4c1C9VLfNnDZWvO_2HQS1rmH8AYbOr0w
linkProvider ProQuest
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3JTsMwEB2xHODCjtixEBwjGk_sOEgIIUop6wHKckCKHMdGCNSyFEE_in_E0yQgLtw4R8lh9iXzHsC61Jhpp0xga96bvFGoIMudCBRKYTnPM2H6aJ9nsnkZHd2ImwH4rG5h6LfKKib2A3XeMTQj30TC0pI-4eDO03NArFG0Xa0oNAqzOLa9d9-yvW4f1r1-Nzhv7Lf2mkHJKhCYJA6DGBOLhDHutMoyKbWQsYus7ztiny4NpykLKuPzrkjQamWFUaiz0LnQ5DF36D87CMMRIhJUv2ocVIFfikSGBXgRYlLb1ASNVRMq_J3yfkf8fhprTMBYWX-y3cJgJmHAtqdgvOJ2YKWrT8Nt3dJ6wSc2dmVfeuza6gd2cX9HcMtbbJed3n_YnJXYtj3W7bC6LzkZjXVZwW9J2n_ssXM6YPfqY-XhExnCDLT-Q2azMNTutO0cMJ5zjBy6yNB-Nvf9d6xzzq3S_rXIZPOwVskqfSrwNlLfp5BA02-BzsNSJcW0dLnX9MdAFv5-vAojzdbpSXpyeHa8CKOcCH2JEwKXYKj78maXfZXRzVb6umWQ_rMtfQFHHOPw
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1NTxsxEB1BkBCXQqEVlC8LwXGVrL32eiuhihIiPiNEgXJAWnn9USFQQiEV5Cf2X3Um8VJx4cZ55T2Mn-d5bM97AJvKiMoEbRPfwtWEoNBJ5YJMtFDSc-4qaUdqn121f5EdXsmrCfhb98LQs8o6J44StetbOiNvCtLSUkg4ohnis4jTdufb_e-EHKToprW20zDRZsFtj-TGYpPHkR8-YTn3uH3Qxrnf4ryzd767n0THgcQWeZrkovCC9MeD0VWllJEqD5nHmiRHKrWcTmCEtsjJshDeaC-tFqZKQ0ity3kQ-NtJmMqpXbQBU9_3uqdnNS0oWah0LG0kRNFqGhLOakmdvibE13wwIrnOHHyIu1O2M4bTR5jwvXmYrZ0fWEwEC3Dd9nT5gLTHLv3DkP305pb9uPlFYsxf2Q47uXn2jkXl2yEb9FkbN6SMDn3Z2P2SsHE3ZGfU3o6Ty2JbFMHkE5y_R9Q-Q6PX7_lFYNxxkQURMku3tw6r89w4zr02OCyz1RJs1LEq78dqHCVWMRTQ8iWgS7BSR7GMC_Kx_A-fL29_XodpxFV5fNA9WoYZTm6_ZBghVqAxePjjV3ELMqjW4uQyKN8ZTv8Apuzuyg
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Detecting+Very+Weak+Signals%3A+A+Mixed+Strategy+to+Deal+with+Biologically+Relevant+Information&rft.jtitle=Algorithms&rft.au=Vici+Alessandro&rft.au=Zeuner%2C+Ann&rft.au=Giuliani+Alessandro&rft.date=2025-09-13&rft.pub=MDPI+AG&rft.eissn=1999-4893&rft.volume=18&rft.issue=9&rft.spage=581&rft_id=info:doi/10.3390%2Fa18090581&rft.externalDBID=HAS_PDF_LINK
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1999-4893&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1999-4893&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1999-4893&client=summon