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Machine Learning

Filter
Guide

What every filter in the HIPPIE filter panel does, and what each source database, experiment type, interaction type and tissue in the lists stands for.

Contents

How filters combine

The protein query, interaction query, network and browse pages share one filter panel; each page shows the subset of controls relevant to it. Hover the icon next to a filter for a short summary, and follow its More details link to the matching section of this page.

  • Filters take effect only when you run or re-apply the search.
  • Different filters combine with logical AND — a result must pass every active filter to be shown.
  • Ticks within one list (sources, experiment types, interaction types, tissues) combine with OR — a result needs to match only one ticked option.
  • The lists start with every option ticked. Clearing a list removes that filter rather than excluding everything, so an unticked list and a fully ticked one return the same results.
  • The number beside each option is counted across all of HIPPIE. It is not recomputed for the subset your other filters leave, so it does not change as you narrow the query. Options that no interaction uses are not listed at all.
  • Protein-level filters (tissue, degree, average score, review status) are checked on the proteins of each interaction. The proteins you query on the protein query page and the seeds on the network page are never removed by them — they apply to the partners that HIPPIE adds.

The same filters are available programmatically; see the REST API.

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Result type

  • Interactions — experimentally supported protein pairs, each with a confidence score.
  • Non-interactions — protein pairs inferred from experimental evidence not to interact. Their rows are drawn on a grey background.
  • Both — interactions and non-interactions together.

Non-interactions carry no source database, experiment type or interaction type. As soon as one of those three lists is narrowed, non-interactions can no longer match and are left out of the result.

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Confidence score

Keeps results whose score lies between a minimum and a maximum bound (0–1); the sliders clamp so that the minimum never exceeds the maximum. How the score is computed is explained under confidence scoring.

The Medium conf. and High conf. presets set the minimum to the current release's median (Q2) and upper-quartile (Q3) score for the selected result type — for interactions currently ≥ 0.63 and ≥ 0.72.

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Source database

Keeps interactions reported by any of the ticked source databases. Many interactions are reported by several sources. Besides the primary interaction databases, the list contains curation teams that deposit their work into IntAct under their own name, and annotation or structure resources that some records name as their origin.

Curated annotation resources
SourceFull nameWhat it isInteractions
UniProt — Interactions annotated by UniProtKB/Swiss-Prot curators and deposited via IntAct. 102139
Curation teams
SourceFull nameWhat it isInteractions
bhf-ucl — Cardiovascular gene-annotation team at UCL that curates interactions of cardiovascular-relevant proteins into IntAct. 1720
mbinfo — Curation team of the MechanoBiology Institute, National University of Singapore, contributing mechanobiology-related interactions to IntAct. 127
Molecular Connections — Commercial curation team (Bangalore, India) that curates interaction data into IntAct. 242
NTNU — Curation team at NTNU (Trondheim) contributing interactions to IntAct. 23
Interaction databases
SourceFull nameWhat it isInteractions
biogrid — Literature-curated protein and genetic interactions across major model organisms and human. 934417
DIP — Experimentally determined protein interactions curated at UCLA (IMEx member). 7680
FlyBase — Drosophila genetics and genomics database; contributes curated interaction records via IntAct. 6
HPIDb — Curated interactions between host and pathogen proteins (Mississippi State University). 322
I2D — Known and predicted protein interactions collected by the Jurisica lab, University of Toronto. 392
InnateDB — Curated interactions and pathways of the innate immune response. 155
intact — Open, literature-curated molecular interaction database hosted at EMBL-EBI; the shared curation platform of the IMEx consortium. 524211
matrixdb — Interactions involving extracellular-matrix proteins, proteoglycans and polysaccharides (University of Lyon). 1496
MINT — Literature-curated protein interactions from the University of Rome Tor Vergata; curated within IntAct (IMEx member). 40712
mpidb — Curated microbial protein interactions; the original site is offline and its data lives on in IntAct. 4
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Experiment type

Keeps interactions detected by any of the ticked experimental methods. Methods are PSI-MI terms grouped into method families; each method links to its definition in the PSI-MI ontology. Every method also carries a quality score that enters the confidence score.

Affinity purification & pull-down (15)
Aggregation & self-assembly (4)
Arrays & display technologies (12)
Binding & biophysical assays (28)
Cleavage & protease assays (6)
Co-fractionation & co-migration (11)
Enzymatic & functional assays (34)
Fluorescence & luminescence readouts (12)
Mass spectrometry (5)
Microscopy & imaging (5)
Proximity labelling & cross-linking (5)
Structural biology (17)
Two-hybrid & complementation (30)
Other (6)
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Interaction type

Keeps interactions classified as any of the ticked interaction types — for example whether two proteins were shown to bind directly, or only to belong to the same complex.

Association & complex membership (2)
  • association 398543
  • physical association 905861
Cleavage (5)
  • cleavage reaction 108
  • dna cleavage 2
  • lipoprotein cleavage reaction 2
  • protein cleavage 121
  • rna cleavage 6
Direct interaction (3)
  • covalent binding 37
  • direct interaction 177863
  • disulfide bond 32
Enzymatic & post-translational reactions (27)
  • acetylation reaction 30
  • adp ribosylation reaction 57
  • ampylation reaction 5
  • atpase reaction 1
  • de-ADP-ribosylation reaction 1
  • deacetylation reaction 27
  • demethylation reaction 10
  • deneddylation reaction 1
  • dephosphorylation reaction 304
  • deubiquitination reaction 13
  • enzymatic reaction 28
  • glycosylation reaction 3
  • gtpase reaction 3
  • guanine nucleotide exchange factor reaction 6
  • hydroxylation reaction 21
  • lipid addition 2
  • methylation reaction 39
  • myristoylation reaction 2
  • neddylation reaction 13
  • oxidoreductase activity electron transfer reaction 11
  • palmitoylation reaction 4
  • phosphorylation reaction 1834
  • phosphotransfer reaction 4
  • proline isomerization reaction 1
  • sumoylation reaction 15
  • transglutamination reaction 1
  • ubiquitination reaction 345
Self-interaction (2)
  • putative self interaction 5
  • self interaction 3
Spatial proximity (2)
  • colocalization 72421
  • proximity 64000
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Tissue expression

Keeps interactions whose proteins are expressed in any of the ticked tissues. Expression is the median gene-level RNA-seq expression from GTEx v11_2025-08-22. Once the tissue list is narrowed, an optional Min. median TPM raises the required expression level. Only genes reaching a median of 1.0 TPM in at least one tissue were imported, so a threshold below 1.0 has no additional effect.

Tissues are grouped by body system and then by organ. The number beside each tissue is how many genes GTEx measures as expressed there — genes, not interactions.

Cardiovascular, blood & immune (7)
  • Artery - Aorta 16589
  • Artery - Coronary 16699
  • Artery - Tibial 16452
  • Heart - Atrial Appendage 16585
  • Heart - Left Ventricle 16296
  • Spleen 16808
  • Whole Blood 15793
Cultured cells (2)
  • Cells - Cultured fibroblasts 15860
  • Cells - EBV-transformed lymphocytes 16249
Digestive system (24)
  • Colon - Sigmoid 16760
  • Colon - Transverse 16976
  • Colon - Transverse - Mixed Cell 16900
  • Colon - Transverse - Mucosa 16728
  • Colon - Transverse - Muscularis 16841
  • Esophagus - Gastroesophageal Junction 16663
  • Esophagus - Mucosa 16757
  • Esophagus - Muscularis 16645
  • Liver 16485
  • Liver - Hepatocyte 15886
  • Liver - Mixed Cell 15947
  • Liver - Portal Tract 16993
  • Minor Salivary Gland 16993
  • Pancreas 16614
  • Pancreas - Acini 16266
  • Pancreas - Islets 16534
  • Pancreas - Mixed Cell 16396
  • Small Intestine - Terminal Ileum 17047
  • Small Intestine - Terminal Ileum - Lymphoid Aggregate 16735
  • Small Intestine - Terminal Ileum - Mixed Cell 17039
  • Stomach 16825
  • Stomach - Mixed Cell 16706
  • Stomach - Mucosa 16399
  • Stomach - Muscularis 16291
Endocrine system (3)
  • Adrenal Gland 16698
  • Pituitary 17124
  • Thyroid 16865
Musculoskeletal, skin & adipose (5)
  • Adipose - Subcutaneous 16688
  • Adipose - Visceral (Omentum) 16741
  • Muscle - Skeletal 16243
  • Skin - Not Sun Exposed (Suprapubic) 16942
  • Skin - Sun Exposed (Lower leg) 16931
Nervous system (14)
  • Brain - Amygdala 16713
  • Brain - Anterior cingulate cortex (BA24) 16773
  • Brain - Caudate (basal ganglia) 16789
  • Brain - Cerebellar Hemisphere 16713
  • Brain - Cerebellum 16806
  • Brain - Cortex 16912
  • Brain - Frontal Cortex (BA9) 16818
  • Brain - Hippocampus 16801
  • Brain - Hypothalamus 16959
  • Brain - Nucleus accumbens (basal ganglia) 16805
  • Brain - Putamen (basal ganglia) 16691
  • Brain - Spinal cord (cervical c-1) 16761
  • Brain - Substantia nigra 16749
  • Nerve - Tibial 16819
Reproductive & breast (9)
  • Breast - Mammary Tissue 16897
  • Cervix - Ectocervix 16879
  • Cervix - Endocervix 16873
  • Fallopian Tube 16887
  • Ovary 16739
  • Prostate 17024
  • Testis 18023
  • Uterus 16741
  • Vagina 16868
Respiratory system (1)
  • Lung 16973
Urinary system (3)
  • Bladder 16800
  • Kidney - Cortex 16869
  • Kidney - Medulla 16904
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Protein filters

  • Min. degree in all of HIPPIE ≥ — the minimum number of interaction partners a protein has across the whole database.
  • Min. avg. score ≥ — the minimum mean confidence score across a protein's interactions.

Both are measured across all of HIPPIE, independently of the source, score and type filters. A protein can therefore pass a high degree threshold and still contribute only a handful of interactions to a narrowly filtered result. For the same reason the median degree in the statistics box of the ML Splits page, which counts only the interactions that survive the filters, is often much lower than the threshold.

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Review status

  • Reviewed — manually curated UniProtKB/Swiss-Prot entries.
  • Unreviewed — automatically annotated UniProtKB/TrEMBL entries.
  • Both — no review-status filter.
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Isoforms

HIPPIE stores interactions both for general protein entries (e.g. P37163) and for individual isoforms (e.g. P37163-2); see Isoforms for background. The three-way filter decides which of them are shown:

  • General — general protein entries only. An isoform still appears when you query it explicitly.
  • Isoforms — only interactions in which at least one partner is a non-canonical isoform.
  • Both — no isoform filter: general proteins and isoforms together.
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Filters on the ML Splits page

The ML Splits page uses the same filters, arranged in two rows: protein filters (tissue expression, degree, average score, isoforms) on top and interaction filters (confidence, experiment type, interaction type, source database) below. A protein that fails the protein filters removes every interaction it takes part in. How the filtered set is turned into train / validation / test data is described in the Machine Learning guide.

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